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array:23 [ "pii" => "S1807593222014156" "issn" => "18075932" "doi" => "10.6061/clinics/2015(03)12" "estado" => "S300" "fechaPublicacion" => "2015-03-01" "aid" => "1415" "copyright" => "CLINICS" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2015;70:220-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemAnterior" => array:19 [ "pii" => "S1807593222014144" "issn" => "18075932" "doi" => "10.6061/clinics/2015(03)11" "estado" => "S300" "fechaPublicacion" => "2015-03-01" "aid" => "1414" "copyright" => "CLINICS" "documento" => "article" "crossmark" => 0 "licencia" => "https://creativecommons.org/licenses/by-nc/3.0/" "subdocumento" => "fla" "cita" => "Clinics. 2015;70:214-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>" "titulo" => "Compensatory sweating after restricting or lowering the level of sympathectomy: a systematic review and meta-analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "214" "paginaFinal" => "219" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 285 "Ancho" => 752 "Tamanyo" => 36134 ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">CS after lowering the level of sympathectomy. CI, confidence interval; CS, compensatory sweating.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Song-Wang Cai, Ning Shen, Dong-Xia Li, Bo Wei, Jun An, Jun-Hang Zhang" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Song-Wang" "apellidos" => "Cai" ] 1 => array:2 [ "nombre" => "Ning" "apellidos" => "Shen" ] 2 => array:2 [ "nombre" => "Dong-Xia" "apellidos" => "Li" ] 3 => array:2 [ "nombre" => "Bo" "apellidos" => "Wei" ] 4 => array:2 [ "nombre" => "Jun" "apellidos" => "An" ] 5 => array:2 [ "nombre" => "Jun-Hang" "apellidos" => "Zhang" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222014144?idApp=UINPBA00004N" "url" => "/18075932/0000007000000003/v1_202212011445/S1807593222014144/v1_202212011445/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">RAPID COMMUNICATION</span>" "titulo" => "Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "220" "paginaFinal" => "227" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Bernadete L Liphaus, Natalia Umetsu, Adriana A Jesus, Silvia Y Bando, Clovis A Silva, Magda Carneiro-Sampaio" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Bernadete L" "apellidos" => "Liphaus" "email" => array:1 [ 0 => "bernadete.liphaus@hc.fm.usp.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Natalia" "apellidos" => "Umetsu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "Adriana A" "apellidos" => "Jesus" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">II</span>" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Silvia Y" "apellidos" => "Bando" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] 4 => array:3 [ "nombre" => "Clovis A" "apellidos" => "Silva" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">II</span>" "identificador" => "aff2" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">III</span>" "identificador" => "aff3" ] ] ] 5 => array:3 [ "nombre" => "Magda" "apellidos" => "Carneiro-Sampaio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade de São Paulo, Instituto da Criança, Laboratório de Investigação Médica 36, São Paulo/SP, Brazil" "etiqueta" => "I" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade de São Paulo, Instituto da Criança, Unidade de Reumatologia, São Paulo/SP, Brazil" "etiqueta" => "II" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Faculdade de Medicina da Universidade de São Paulo, Disciplina de Reumatologia, São Paulo/SP, Brazil" "etiqueta" => "III" "identificador" => "aff3" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "corresponding author" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 856 "Ancho" => 745 "Tamanyo" => 107718 ] ] "descripcion" => array:1 [ "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Type I C2 deficiency in juvenile systemic lupus erythematosus patients 2 (P2) and 3 (P3). A – Nucleotide sequence alignment for P2 and P3; B and C – Nucleotide chromatograms for P2 and P3, respectively. NG_11730.1 is the reference DNA sequence for C2, and NG_11730 is the codified sequence for C2 (final region of exon 6). The blue arrow indicates the last nucleotide of exon 6, and the red arrow indicates the initial deletion site; D – Agarose gel electrophoresis showing the heterozygous 28 bp deletion in exon 6 of the C2 gene. Lane 1: 100 bp DNA ladder; lane 2: P2; lane 3: P3; lane 4: positive control; lane 5: negative control. The blue and red arrows indicate the 174 bp and 146 bp fragments, respectively.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Inherited deficiencies of the complement components C1q, C2 and C4 are frequently associated with the development of systemic lupus erythematosus (SLE) due to the impaired clearance of apoptotic debris, a decreased capacity for immune-complex handling, and/or their role in peripheral B-cell tolerance <a class="elsevierStyleCrossRefs" href="#bib1">1-9</a>.</p><p id="para20" class="elsevierStylePara elsevierViewall">Homozygous C1q deficiency is the strongest genetic risk factor related to SLE <a class="elsevierStyleCrossRef" href="#bib3">3</a>,. Similarly, both Type I and II C2 deficiency have been associated with SLE <a class="elsevierStyleCrossRef" href="#bib4">4</a>,. In addition, homozygous C4A deficiency is approximately 10 times more frequent in patients with SLE <a class="elsevierStyleCrossRef" href="#bib4">4</a>,.</p><p id="para30" class="elsevierStylePara elsevierViewall">Few studies have evaluated the non-coding regions and mRNA expression of complement genes. Furthermore, complement deficiencies are rare among SLE patients but are common among patients with juvenile SLE (JSLE) <a class="elsevierStyleCrossRef" href="#bib23">23</a>.</p><p id="para40" class="elsevierStylePara elsevierViewall">We previously showed an underlying primary complement deficiency in seven JSLE patients <a class="elsevierStyleCrossRef" href="#bib3">3</a>. We had access to DNA samples and/or peripheral cells from four of these patients, and to better understand these inherited deficiencies, we conducted a molecular characterization of the C1q, C2 and C4 genes.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><p id="para50" class="elsevierStylePara elsevierViewall">Among 72 JSLE patients, 16 had primary immunodeficiency, and seven of the 16 were determined to have complement deficiency based on a combination of low or undetectable serum levels of C1q, or C1s, C1r, C2, C3 or C4 with normal levels of the other components in at least two samples and low activity/inactive disease (SLEDAI-2K score<4) <a class="elsevierStyleCrossRef" href="#bib3">3</a>. Therefore, we selected four patients: patient 1 (P1) had undetectable serum C1q, normal C3 and C4 levels, negative anti-C1q and available DNA and mononuclear cells; patient 2 (P2) had decreased IgA, C2 and C4 serum levels and stored DNA but no cells available for culture; patient 3 (P3) had decreased C2 and normal C3 and C4 levels; and patient 4 (P4) had repeated decreased C4 and normal C1q, C2 and C3 levels and peripheral cells available for culture (<a class="elsevierStyleCrossRefs" href="#tbl1">Tables 1 and 2</a>). Three healthy controls matched by age and gender and with normal complement levels were also enrolled. Patients fulfilled the revised American College of Rheumatology classification criteria, and informed consent was obtained for all participants after the local ethics committee had approved the study <a class="elsevierStyleCrossRef" href="#bib24">24</a>,<a class="elsevierStyleCrossRef" href="#bib25">25</a>.</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para60" class="elsevierStylePara elsevierViewall">We previously determined the C4 gene copy number by quantitative real-time polymerase chain reaction (qRT-PCR), as reported <a class="elsevierStyleCrossRef" href="#bib3">3</a>,<a class="elsevierStyleCrossRef" href="#bib26">26</a> (<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>).</p><p id="para70" class="elsevierStylePara elsevierViewall">All exons and 3′ and 5′ non-coding regions (UTR) of the C1q and C2 genes (3 exons each for the C1q A, B, and C chains and 18 exons for the C2 gene) were sequenced. Primers (Supplementary Table) were designed using the reference sequences deposited in GenBank (NG_007282.1 for C1qA, NG_007283.1 for C1qB, NG_007565.1 for C1qC and NG_011730.1 for C2) with the <span class="elsevierStyleItalic">Primer-BLAST</span> program. DNA was obtained using the QIAamp DNA Blood Midi kit (N°51104 Qiagen, Hilden, Germany), and purity and concentration were determined with a <span class="elsevierStyleItalic">Nanovue</span>® spectrophotometer (GE Healthcare, USA). Each PCR reaction was performed in a final volume of 25 µl containing 100 ng of DNA, 20 mM Tris-HCl (pH 8.4), 50 mM KCl, 2.0 mM MgSO4, 100 µM each of dATP, dCTP, dGTP and dTTP, 0.5 µM of each primer and 1.5 U of High-Fidelity Platinum Taq DNA Polymerase (Invitrogen, Carlsbad, CA, USA). The amplification conditions included 35 cycles of 95°C for 30 s, 60°C for 30 s and 72°C for 2 min, with an initial denaturing step of 95°C for 5 min and a final extension step of 72°C for 7 min. Products were purified using the GFX PCR DNA and Gel Band Purification Kit (GE Healthcare Life Science, UK). Amplicons and primers were sent to Centro de Estudos do Genoma Humano for sequencing. The BioEdit and ClustalW sequence alignment editors (http://www.mbio.ncsu.edu/bioedit/bioedit.html) were used to align the nucleotide sequences. The BLAST program (http://blast.ncbi.nlm.nih.gov/Blast.cgi) was used to search variant sequences obtained from the human genomic database. The Chromas software program was used for chromatogram visualization. Type I C2 deficiency was evaluated by PCR as previously described and confirmed by gene sequencing <a class="elsevierStyleCrossRef" href="#bib3">3</a>,<a class="elsevierStyleCrossRef" href="#bib27">27</a>.</p><p id="para80" class="elsevierStylePara elsevierViewall">The quantitative analysis of C1q, C2 and C4 mRNA was performed using peripheral mononuclear cells obtained by centrifugation using Ficoll-Paque Plus (GE Healthcare, Piscataway, NJ, USA) and cultured in supplemented DMEM medium (10% fetal bovine serum, 10,000 U/ml penicillin and 100 g/ml streptomycin) at 37°C with 5% CO<span class="elsevierStyleInf">2</span> for 36 hours. Parallel cultures were stimulated with 100 U/µl of recombinant human interferon gamma (IFNγ; N°300-02 Preprotech, Rocky Hill, NJ, USA) as previously described <a class="elsevierStyleCrossRef" href="#bib28">28</a>. RNA was obtained from cultures using an RNeasy Midi Kit (N°74104, Qiagen, Hilden, Germany). RNA (500 ng) was reverse-transcribed to produce complementary DNA (cDNA) using the <span class="elsevierStyleItalic">SuperScript III First-Strand Synthesis System for RT-PCR</span> (N°18080-051, Invitrogen, Carlsbad, CA, USA). The qRT-PCR was performed using 2 µl of cDNA, 1 µM each of forward and reverse primers and 1X <span class="elsevierStyleItalic">SYBR Green Mix QuantiFast PCR Kit</span> (N°204054, Qiagen, Hilden, Germany) in a StepOnePlus Real-Time PCR System (Applied Biosystems, Forrest City, CA, USA). The cycling parameters included an initial 15 min hot start at 95°C, followed by 50 cycles of 15 s at 95°C and 30 s at 60°C. C4B primers were designed based on a GenBank reference sequence (NG_011638, Supplementary Table). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as an endogenous reference gene for qRT-PCR reaction normalization. Relative expression (RE) was determined by the standard curve method, and mean values are presented here as relative variation expression (RVE) obtained from RVE = target gene RE – GAPDH RE.</p><p id="para90" class="elsevierStylePara elsevierViewall">A t-test was used to compare the control and untreated samples and the patient treated and untreated samples. p<0.05 was considered significant.</p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">RESULTS</span><p id="para100" class="elsevierStylePara elsevierViewall">C1q gene sequencing (P1) revealed a heterozygous silent mutation in exon 3 of the A chain (c.276 A>G Gly), a homozygous single-base change in the 3′ UTR of the B chain (c*78 A>G), and a heterozygous silent mutation in exon 2 of the C chain (c.126 C>T Pro) (<a class="elsevierStyleCrossRef" href="#fig1">Figures 1</a>,<a class="elsevierStyleCrossRef" href="#fig2">2</a>,<a class="elsevierStyleCrossRef" href="#fig3">3</a>). The qRT-PCR analysis revealed that C1qA mRNA expression was decreased compared with that of healthy controls (p<0.05) and was also decreased after IFNγ stimulation (treated cells) compared with that of non-treated cells; C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation, and C1qC mRNA expression was increased compared with that of controls and was even higher after IFNγ stimulation (<a class="elsevierStyleCrossRef" href="#fig5">Figure 5A</a>).</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="fig3"></elsevierMultimedia><elsevierMultimedia ident="fig5"></elsevierMultimedia><p id="para110" class="elsevierStylePara elsevierViewall">P1's healthy mother had an identical but homozygous silent mutation in the A chain, a homozygous single-base change in the B chain, a heterozygous silent mutation in the C chain, and an additional missense mutation in the A chain (c. 295 A>C Ile-Leu) (<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>). The peripheral cells of the mother were not available for mRNA expression.</p><p id="para120" class="elsevierStylePara elsevierViewall">P2 and P3 had a heterozygous 28 bp deletion at exon 6, characterizing Type I C2 deficiency, as shown in <a class="elsevierStyleCrossRef" href="#fig4">Figure 4</a>. The C2 mRNA expression (P3) was 23 times lower compared with that of controls and did not change after IFNγ stimulation (<a class="elsevierStyleCrossRef" href="#fig5">Figure 5B</a>).</p><elsevierMultimedia ident="fig4"></elsevierMultimedia><p id="para130" class="elsevierStylePara elsevierViewall">The C4B mRNA expression in P4 was significantly decreased compared with that of controls and increased after IFNγ stimulation (<a class="elsevierStyleCrossRef" href="#fig5">Figure 5C</a>). The C4A mRNA expression was not technically adequate, and it was therefore not considered for analysis.</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">DISCUSSION</span><p id="para140" class="elsevierStylePara elsevierViewall">For the first time in JSLE patients, we showed heterozygous silent mutations, a homozygous single-base change in the 3′ UTR and decreased mRNA expression for the C1q gene; a heterozygous Type I deficiency and decreased mRNA expression for the C2 gene; and decreased mRNA expression for the C4B gene.</p><p id="para150" class="elsevierStylePara elsevierViewall">Although complement deficiencies were the first identified genetic risk factors for SLE, it remains unclear how these deficiencies should be assessed <a class="elsevierStyleCrossRef" href="#bib2">2-4</a>,<a class="elsevierStyleCrossRef" href="#bib3">7</a>,<a class="elsevierStyleCrossRef" href="#bib4">8</a>,<a class="elsevierStyleCrossRef" href="#bib7">27</a>,.</p><p id="para160" class="elsevierStylePara elsevierViewall">Studies have described nonsense and missense mutations in the C1q gene, with a total of 12 causative mutations <a class="elsevierStyleCrossRef" href="#bib3">3-5</a>,<a class="elsevierStyleCrossRef" href="#bib4">10-12</a>,<a class="elsevierStyleCrossRef" href="#bib5">23</a>,. Single nucleotide polymorphisms and silent mutations have also been described <a class="elsevierStyleCrossRef" href="#bib12">12</a>,<a class="elsevierStyleCrossRef" href="#bib38">38</a>. However, although there were no amino acid changes due to the identified base changes, the mRNA expression of the C1qA, B and C chains was altered. There is evidence that silent mutations can influence gene expression via alternative splicing by altering the exonic splicing enhancer or silencer sites <a class="elsevierStyleCrossRef" href="#bib39">39</a>. There is no evidence that heterozygous mutations of the C1q gene can lead to lupus if the other allele is normal. Of note, our patient presented photosensitivity, which is a characteristic associated with a single-nucleotide change in the C1qA gene <a class="elsevierStyleCrossRef" href="#bib38">38</a>. In addition, Rafiq reported allelic variance in the 3′ UTR of the C1qB chain associated with low C1q serum levels <a class="elsevierStyleCrossRef" href="#bib36">36</a>. The fact that the 3′ UTR single-base change in C1qB was homozygous implies that the mother and father each have one allele with the same sequence variants. P1's mother had normal C1q levels and did not present any symptoms of autoimmune disease; however, she harbored silent mutations with an additional missense mutation in the A chain. Because the C1q protein was present in P1's mother, it becomes questionable whether the observed variants are, by themselves, pathogenic <a class="elsevierStyleCrossRef" href="#bib40">40</a>,<a class="elsevierStyleCrossRef" href="#bib41">41</a>. Peripheral cells from the patient's father and mother were not available for mRNA expression analysis, which could have addressed on the latter speculation.</p><p id="para170" class="elsevierStylePara elsevierViewall">An intriguing aspect of these results was the observation of mRNA expression from the C1q chains after IFNγ stimulation. IFNγ is able to induce and up-regulate complement production by monocytes <a class="elsevierStyleCrossRef" href="#bib28">28</a>,<a class="elsevierStyleCrossRef" href="#bib42">42</a>,<a class="elsevierStyleCrossRef" href="#bib43">43</a>. C1qA and B expression was decreased, and C1qC was increased, which suggests deregulated production that could influence the heterotrimeric assembly of protein. Nanjou et al. demonstrated that only one defect in any C1q chain can compromise the entire synthesis and secretion of the C1q protein <a class="elsevierStyleCrossRef" href="#bib37">37</a>. Because mRNA was still expressed, it is unlikely that the observed base changes could completely block protein expression, and alternative causes must be considered. Therefore, further work assessing mRNA stability and translation efficiency will be needed.</p><p id="para180" class="elsevierStylePara elsevierViewall">Type I C2 deficiency is due to a 9 bp deletion from the 3′ end of exon 6 and a 19 bp deletion from the 5′ region of the following intron, leading to a frame shift and a premature stop codon <a class="elsevierStyleCrossRef" href="#bib2">2</a>,<a class="elsevierStyleCrossRef" href="#bib13">13</a>,<a class="elsevierStyleCrossRef" href="#bib15">15</a>,<a class="elsevierStyleCrossRef" href="#bib16">16</a>,<a class="elsevierStyleCrossRef" href="#bib29">29</a>. More than half of individuals with primary C2 deficiency develop SLE or lupus-like disease <a class="elsevierStyleCrossRef" href="#bib2">2</a>,<a class="elsevierStyleCrossRef" href="#bib29">29</a>. C2 gene sequencing was performed because most Type I deficiencies associated with SLE are homozygous and because Zhu et al. have reported a compound heterozygous Type I and II C2 deficiency in an African-American family <a class="elsevierStyleCrossRef" href="#bib14">14-16</a>,.</p><p id="para190" class="elsevierStylePara elsevierViewall">Although the Type I C2 deficiency was heterozygous, it resulted in a 23-fold reduction in mRNA expression. Lipsker et al. observed decreased but still detectable C2 levels in SLE patients with a heterozygous Type I C2 deficiency <a class="elsevierStyleCrossRef" href="#bib43">43</a>. Our findings raise both (1) the possibility that heterozygous C2 mutations alone or in combination with other factors could lead to SLE and (2) the question of why C2 mRNA expression was so low when the patient still had one functional C2 gene. Therefore, further JSLE patients with decreased C2 serum levels should be evaluated for Type I C2 deficiency to better understand the relationship of this condition with the disease.</p><p id="para200" class="elsevierStylePara elsevierViewall">The C4A and C4B genes each have 41 exons and differ from each other by only five nucleotides. The number of gene copies ranges from two to eight, and deficiencies in these two genes have been associated with SLE <a class="elsevierStyleCrossRef" href="#bib18">18-20</a>,<a class="elsevierStyleCrossRef" href="#bib19">44</a>,. P4 had persistently low C4 serum levels, with two copies of C4A and three of C4B; the C4B mRNA expression in this individual was significantly decreased compared with controls and increased after IFNγ stimulation. Although this was an interesting finding, attributing the abnormal C4B mRNA expression to a gene mutation requires presuming that there were mutations in most or all of her three copies, which is possible but unlikely. Additionally, we would presume that there was a simultaneous problem with C4A transcription, which could not be evaluated. Thus, further work is needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.</p><p id="para210" class="elsevierStylePara elsevierViewall">This study was unprecedented because it involved the sequencing of all exons and non-coding regions of the C1q and C2 genes as well as the evaluation of mRNA expression. The limitations included the small number of patients, which created the need for experimental replicates, and the need for fresh mononuclear cells for mRNA expression analysis.</p><p id="para220" class="elsevierStylePara elsevierViewall">In conclusion, silent mutations and single-base changes in the 3′ non-coding region may modulate mRNA transcription and C1q production; Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels; and further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">AUTHOR CONTRIBUTIONS</span><p id="para230" class="elsevierStylePara elsevierViewall">All authors drafted, critically reviewed for intellectual content and approved the final version of the manuscript. Liphaus BL contributed to study conception and design, data analysis and interpretation and manuscript writing. Umetsu N contributed to data acquisition, analysis and interpretation. Jesus AA contributed to data acquisition, analysis and interpretation. Bando SY contributed to data analysis and interpretation and manuscript writing. Silva CA contributed to patient enrollment and data acquisition. Carneiro-Sampaio M contributed to study conception, data interpretation and manuscript intellectual content.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1582430" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:2 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" ] 3 => array:2 [ "identificador" => "cesec30" "titulo" => "RESULTS" ] 4 => array:2 [ "identificador" => "cesec40" "titulo" => "DISCUSSION" ] 5 => array:2 [ "identificador" => "cesec50" "titulo" => "AUTHOR CONTRIBUTIONS" ] 6 => array:2 [ "identificador" => "xack639329" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-08-14" "fechaAceptado" => "2015-01-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1582430" "palabras" => array:5 [ 0 => "Juvenile systemic lupus erythematosus" 1 => "Complement deficiency" 2 => "C1q, C2 and C4 genes" 3 => "Silent mutation" 4 => "Non-coding region" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE:</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus.</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS:</span><p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction.</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS:</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3′ non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation.</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS:</span><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">Silent mutations and single-base changes in the 3′ non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "ceabs10" "titulo" => "OBJECTIVE:" ] 1 => array:2 [ "identificador" => "ceabs20" "titulo" => "METHODS:" ] 2 => array:2 [ "identificador" => "ceabs30" "titulo" => "RESULTS:" ] 3 => array:2 [ "identificador" => "ceabs40" "titulo" => "CONCLUSIONS:" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported.</p>" ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 539 "Ancho" => 670 "Tamanyo" => 90771 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">C1qA gene sequencing from juvenile systemic lupus erythematosus patient 1 (P1) and P1's mother. A – Nucleotide sequence alignment for P1 and P1's mother; B – Amino acid sequence for P1 and P1's mother; C and D – Nucleotide chromatograms of P1 and P1's mother, respectively. NG_007282.1 is the reference codified sequence for C1qA. The arrows indicate the variation sites (exon 3, c.276 A>G Gly; c.295 A>C Ile-Leu).</p>" ] ] 1 => array:7 [ "identificador" => "fig2" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 461 "Ancho" => 670 "Tamanyo" => 57964 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">C1qB gene sequencing from juvenile systemic lupus erythematosus patient 1 (P1) and P1's mother. A – Nucleotide sequence alignment for P1 and P1's mother; B and C – Nucleotide chromatograms of P1 and P1's mother, respectively. NG_007283.1 is the reference codified or mRNA sequence for C1qB. The arrow indicates the variation site (3′ UTR c*78 A>G).</p>" ] ] 2 => array:7 [ "identificador" => "fig3" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 648 "Ancho" => 664 "Tamanyo" => 69453 ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">C1qC gene sequencing from juvenile systemic lupus erythematosus patient 1 (P1) and P1's mother. A – Nucleotide sequence alignment for P1 and P1's mother; B and C – Nucleotide chromatograms of P1 and P1's mother, respectively. NG_007565.1 is the reference codified sequence for C1qC. The arrow indicates the variation site (exon 2, c.126 C>T Pro).</p>" ] ] 3 => array:7 [ "identificador" => "fig4" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 856 "Ancho" => 745 "Tamanyo" => 107718 ] ] "descripcion" => array:1 [ "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Type I C2 deficiency in juvenile systemic lupus erythematosus patients 2 (P2) and 3 (P3). A – Nucleotide sequence alignment for P2 and P3; B and C – Nucleotide chromatograms for P2 and P3, respectively. NG_11730.1 is the reference DNA sequence for C2, and NG_11730 is the codified sequence for C2 (final region of exon 6). The blue arrow indicates the last nucleotide of exon 6, and the red arrow indicates the initial deletion site; D – Agarose gel electrophoresis showing the heterozygous 28 bp deletion in exon 6 of the C2 gene. Lane 1: 100 bp DNA ladder; lane 2: P2; lane 3: P3; lane 4: positive control; lane 5: negative control. The blue and red arrows indicate the 174 bp and 146 bp fragments, respectively.</p>" ] ] 4 => array:7 [ "identificador" => "fig5" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1250 "Ancho" => 784 "Tamanyo" => 56921 ] ] "descripcion" => array:1 [ "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Relative expression of mRNA in cells from juvenile systemic lupus erythematosus patients and controls and after in vitro IFN-γ stimulation (treated). A – The relative expression of the C1q A, B and C chains in P1's cells; B – The relative expression of C2 in P3's cells; C – The relative expression of C4B in P4's cells. RVE – relative variation expression. *indicates a significant difference, p<0.05.</p>" ] ] 5 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="tfn1" class="elsevierStyleSimplePara elsevierViewall">*There was neither patient with C1r or C1s alterations, nor with persistent low C3 levels.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">C1q (33-209 mg/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">C2 (14-25 mg/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">C3 (0.5-1.8 g/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">C4 (0.1-0.4 g/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">C4 copy number \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><span class="elsevierStyleBold">0.0/0.0</span> (anti-C1q -) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">8.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Not done \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">135.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><span class="elsevierStyleBold">4.1/0.0</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">1.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><span class="elsevierStyleBold">0.0/0.08</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 copies C4A 1 copy C4B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">4.6/12 (anti-C1q +) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><span class="elsevierStyleBold">3.4/14</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">1.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">Not done \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">38.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top"><span class="elsevierStyleBold">0.04/0.05</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">2 copies C4A 3 copies C4B \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">-Complement component values from four juvenile systemic lupus erythematosus patients selected for molecular characterization from a cohort of seven patients previously determined to have primary complement deficiencies.</p>" ] ] 6 => array:7 [ "identificador" => "tbl2" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="top" scope="col">Patient/complement deficiency \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Gender \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Age at diagnosis (years) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="top" scope="col">Clinical and laboratory findings/Evolution \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P1/C1q</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Photosensitivity, membranous glomerulonephritis, positive ANA, anti-dsDNA, anti-Sm, anti-RNP and anti-La/lost for follow-up \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P2/C2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Diffuse proliferaitive glomerulonephritis, thrombocytopenia, positive ANA, anti-Ro, and anti-La. A brother with SLE and mother with Sjögren's syndrome/dead \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P3/C2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Serositis, arthritis, lymphopenia, photosensitivity, alopecia, oral ulcers, positive ANA and anti-dsDNA/follow-up \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top"><span class="elsevierStyleBold">P4/C4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="top">female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Arthritis, serositis, seizures, hemolytic anemia, lymphopenia, positive ANA and anti-dsDNA/follow-up \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Clinical and laboratory findings from four juvenile systemic lupus erythematosus patients with primary complement deficiencies who were selected for molecular characterization <a class="elsevierStyleCrossRef" href="#bib3">3</a>.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of disease: Systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ A Rahman \n \t\t\t\t\t\t\t\t """ 1 => """ DA Isenberg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra071297" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2008" "volumen" => "358" "numero" => "9" "paginaInicial" => "929" "paginaFinal" => "939" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18305268" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ M Carneiro-Sampaio \n \t\t\t\t\t\t\t\t """ 1 => """ BL Liphaus \n \t\t\t\t\t\t\t\t """ 2 => """ AA Jesus \n \t\t\t\t\t\t\t\t """ 3 => """ CAA Silva \n \t\t\t\t\t\t\t\t """ 4 => """ JB Oliveira \n \t\t\t\t\t\t\t\t """ 5 => """ MH Kiss \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1007/s10875-008-9187-2" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "2008" "volumen" => "28" "paginaInicial" => "S34" "paginaFinal" => "S41" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18404362" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1007/s10875-008-9187-2" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1007/s10875-008-9187-2" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ AA Jesus \n \t\t\t\t\t\t\t\t """ 1 => """ BL Liphaus \n \t\t\t\t\t\t\t\t """ 2 => """ CA Silva \n \t\t\t\t\t\t\t\t """ 3 => """ SY Bando \n \t\t\t\t\t\t\t\t """ 4 => """ LEC Andrade \n \t\t\t\t\t\t\t\t """ 5 => """ A Coutinho \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1177/0961203311411598" "Revista" => array:7 [ "tituloSerie" => "Lupus" "fecha" => "2011" "volumen" => "20" "numero" => "12" "paginaInicial" => "1275" "paginaFinal" => "1284" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21813590" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1177/0961203311411598" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1177/0961203311411598" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of complement in the development of systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ AP Manderson \n \t\t\t\t\t\t\t\t """ 1 => """ M Botto \n \t\t\t\t\t\t\t\t """ 2 => """ MJ Walport \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann Rev Immunol" "fecha" => "2004" "volumen" => "22" "paginaInicial" => "431" "paginaFinal" => "456" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1146/annurev.immunol.22.012703.104549" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic lupus erythematosus, complement deficiency, and apoptosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ MC Pickering \n \t\t\t\t\t\t\t\t """ 1 => """ M Botto \n \t\t\t\t\t\t\t\t """ 2 => """ PR Taylor \n \t\t\t\t\t\t\t\t """ 3 => """ PJ Lachmann \n \t\t\t\t\t\t\t\t """ 4 => """ MJ Walport \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/s0065-2776(01)76021-x" "Revista" => array:6 [ "tituloSerie" => "Adv Immunol" "fecha" => "2001" "volumen" => "76" "paginaInicial" => "227" "paginaFinal" => "324" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11079100" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/s0065-2776(01)76021-x" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0065-2776(01)76021-X" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of apoptosis proteins and complement components in the eiophatogenesis of systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ BL Liphaus \n \t\t\t\t\t\t\t\t """ 1 => """ MH Bittencourt Kiss \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1590/S1807-59322010000300014" "Revista" => array:7 [ "tituloSerie" => "Clinics" "fecha" => "2010" "volumen" => "65" "numero" => "3" "paginaInicial" => "327" "paginaFinal" => "333" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20360925" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1590/S1807-59322010000300014" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1590/S1807-59322010000300014" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C1q deficiency and juvenile-onset systemic lupus erythematosus: report of two Brazilian cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ AA Jesus \n \t\t\t\t\t\t\t\t """ 1 => """ BL Liphaus \n \t\t\t\t\t\t\t\t """ 2 => """ G Porta \n \t\t\t\t\t\t\t\t """ 3 => """ MH Kiss \n \t\t\t\t\t\t\t\t """ 4 => """ CA Silva \n \t\t\t\t\t\t\t\t """ 5 => """ M Carneiro-Sampaio \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2008.03767.x" "Revista" => array:7 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2008" "volumen" => "154" "numero" => "154 Suppl 1" "paginaInicial" => "1" "paginaFinal" => "224" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18954329" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complement deficiencies and systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ L Truedsson \n \t\t\t\t\t\t\t\t """ 1 => """ AA Bengtsson \n \t\t\t\t\t\t\t\t """ 2 => """ G Sturfelt \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1080/08916930701510673" "Revista" => array:7 [ "tituloSerie" => "Autoimmunity" "fecha" => "2007" "volumen" => "40" "numero" => "8" "paginaInicial" => "560" "paginaFinal" => "566" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18075790" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1080/08916930701510673" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1080/08916930701510673" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between systemic Lupus erythematosus and deficiencies of the complement system" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ S Goerg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Cell Mol Biol" "fecha" => "2002" "volumen" => "48" "numero" => "3" "paginaInicial" => "237" "paginaFinal" => "245" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12030427" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ L Schejbel \n \t\t\t\t\t\t\t\t """ 1 => """ L Skattum \n \t\t\t\t\t\t\t\t """ 2 => """ S Hagelberg \n \t\t\t\t\t\t\t\t """ 3 => """ A Ahlin \n \t\t\t\t\t\t\t\t """ 4 => """ B Schiller \n \t\t\t\t\t\t\t\t """ 5 => """ S Berg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/gene.2011.39" "Revista" => array:7 [ "tituloSerie" => "Genes Immunity" "fecha" => "2011" "volumen" => "12" "numero" => "8" "paginaInicial" => "626" "paginaFinal" => "634" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21654842" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/gene.2011.39" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1038/gene.2011.39" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular basis of hereditary C1q deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ F Petry \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Immunobiol" "fecha" => "1998" "volumen" => "199" "numero" => "2" "paginaInicial" => "286" "paginaFinal" => "294" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0171-2985(98)80033-8" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Common silent mutations in all types of hereditary complement C1q deficiencies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ F Petry \n \t\t\t\t\t\t\t\t """ 1 => """ M Loos \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1007/s00251-005-0023-z" "Revista" => array:7 [ "tituloSerie" => "Immunogenetics" "fecha" => "2005" "volumen" => "57" "numero" => "8" "paginaInicial" => "566" "paginaFinal" => "571" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16086173" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1007/s00251-005-0023-z" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1007/s00251-005-0023-z" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of the Type-I Complement C2 Deficiency Gene in Swedish Systemic Lupus Erythematosus Patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ L Truedsson \n \t\t\t\t\t\t\t\t """ 1 => """ G Sturfelt \n \t\t\t\t\t\t\t\t """ 2 => """ O Nived \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1177/096120339300200509" "Revista" => array:7 [ "tituloSerie" => "Lupus" "fecha" => "1993" "volumen" => "2" "numero" => "5" "paginaInicial" => "325" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8305927" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1177/096120339300200509" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1177/096120339300200509" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel type II complement C2 deficiency allele in an African-American family" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ ZB Zhu \n \t\t\t\t\t\t\t\t """ 1 => """ TP Atkinson \n \t\t\t\t\t\t\t\t """ 2 => """ JE Volanakis \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Immunol" "fecha" => "1998" "volumen" => "161" "numero" => "2" "paginaInicial" => "578" "paginaFinal" => "584" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9670930" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of Type-I Complement C2 Deficiency MHC Haplotypes - Strong Conservation of the Complotype/HLA-B-Region and Absence of Disease Association due to Linked Class-II Genes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ L Truedsson \n \t\t\t\t\t\t\t\t """ 1 => """ CA Alper \n \t\t\t\t\t\t\t\t """ 2 => """ ZL Awdeh \n \t\t\t\t\t\t\t\t """ 3 => """ P Johansen \n \t\t\t\t\t\t\t\t """ 4 => """ AG Sjoholm \n \t\t\t\t\t\t\t\t """ 5 => """ G Sturfelt \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Immunol" "fecha" => "1993" "volumen" => "151" "numero" => "10" "paginaInicial" => "5856" "paginaFinal" => "5863" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7901282" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Type-I Human-Complement C2 Deficiency - A 28-base pair Gene Deletion Causes Skipping of Exon-6 During RNA Splicing" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ CA Johnson \n \t\t\t\t\t\t\t\t """ 1 => """ P Densen \n \t\t\t\t\t\t\t\t """ 2 => """ RK Hurford \n \t\t\t\t\t\t\t\t """ 3 => """ HR Colten \n \t\t\t\t\t\t\t\t """ 4 => """ RA Wetsel \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "1992" "volumen" => "267" "numero" => "13" "paginaInicial" => "9347" "paginaFinal" => "9353" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1577763" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Type II human complement C2 deficiency - Allele-specific amino acid substitutions (Ser(189)->Phe;Gly(444)->Arg) cause impaired C2 secretion" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ RA Wetsel \n \t\t\t\t\t\t\t\t """ 1 => """ J Kulics \n \t\t\t\t\t\t\t\t """ 2 => """ ML Lokki \n \t\t\t\t\t\t\t\t """ 3 => """ P Kiepiela \n \t\t\t\t\t\t\t\t """ 4 => """ H Akama \n \t\t\t\t\t\t\t\t """ 5 => """ CAC Johnson \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1074/jbc.271.10.5824" "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "1996" "volumen" => "271" "numero" => "10" "paginaInicial" => "5824" "paginaFinal" => "5831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8621452" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1074/jbc.271.10.5824" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1074/jbc.271.10.5824" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ Y Yang \n \t\t\t\t\t\t\t\t """ 1 => """ K Lhotta \n \t\t\t\t\t\t\t\t """ 2 => """ EK Chung \n \t\t\t\t\t\t\t\t """ 3 => """ P Eder \n \t\t\t\t\t\t\t\t """ 4 => """ F Neumair \n \t\t\t\t\t\t\t\t """ 5 => """ CY Yu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.4049/jimmunol.173.4.2803" "Revista" => array:7 [ "tituloSerie" => "J Immunol" "fecha" => "2004" "volumen" => "173" "numero" => "4" "paginaInicial" => "2803" "paginaFinal" => "2814" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15294999" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.4049/jimmunol.173.4.2803" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.4049/jimmunol.173.4.2803" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The molecular basis of complete complement C4A and C4B deficiencies in a systemic lupus erythematosus patient with homozygous C4A and C4B mutant genes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ KL Rupert \n \t\t\t\t\t\t\t\t """ 1 => """ JM Moulds \n \t\t\t\t\t\t\t\t """ 2 => """ Y Yang \n \t\t\t\t\t\t\t\t """ 3 => """ FC Arnett \n \t\t\t\t\t\t\t\t """ 4 => """ RW Warren \n \t\t\t\t\t\t\t\t """ 5 => """ JD Reveille \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.4049/jimmunol.169.3.1570" "Revista" => array:7 [ "tituloSerie" => "J Immunol" "fecha" => "2002" "volumen" => "169" "numero" => "3" "paginaInicial" => "1570" "paginaFinal" => "1578" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12133986" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.4049/jimmunol.169.3.1570" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.4049/jimmunol.169.3.1570" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular basis of complete complement C4 deficiency in two North-African families with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ YL Wu \n \t\t\t\t\t\t\t\t """ 1 => """ G Hauptmann \n \t\t\t\t\t\t\t\t """ 2 => """ M Viguier \n \t\t\t\t\t\t\t\t """ 3 => """ CY Yu \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/gene.2009.10" "Revista" => array:7 [ "tituloSerie" => "Genes Immunity" "fecha" => "2009" "volumen" => "10" "numero" => "5" "paginaInicial" => "433" "paginaFinal" => "445" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19279649" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/gene.2009.10" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1038/gene.2009.10" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): Low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ Y Yang \n \t\t\t\t\t\t\t\t """ 1 => """ EK Chung \n \t\t\t\t\t\t\t\t """ 2 => """ YL Wu \n \t\t\t\t\t\t\t\t """ 3 => """ SL Savelli \n \t\t\t\t\t\t\t\t """ 4 => """ HN Nagaraja \n \t\t\t\t\t\t\t\t """ 5 => """ B Zhou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genetics" "fecha" => "2007" "volumen" => "80" "numero" => "6" "paginaInicial" => "1037" "paginaFinal" => "1054" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low gene copy number for c4, c4a and c4b is a strong risk factor for developing systemic lupus erythematosus in childhood" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ LEC Andrade \n \t\t\t\t\t\t\t\t """ 1 => """ KMC Pereira \n \t\t\t\t\t\t\t\t """ 2 => """ AGA Faria \n \t\t\t\t\t\t\t\t """ 3 => """ B Liphaus \n \t\t\t\t\t\t\t\t """ 4 => """ AA Jesus \n \t\t\t\t\t\t\t\t """ 5 => """ C Silva \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arthitis Rheum" "fecha" => "2012" "volumen" => "64" "numero" => "10" "paginaInicial" => "S965" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complete complement deficiency in a large cohort of familial systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ R Aggarwal \n \t\t\t\t\t\t\t\t """ 1 => """ AL Sestak \n \t\t\t\t\t\t\t\t """ 2 => """ A D′Sousa \n \t\t\t\t\t\t\t\t """ 3 => """ SP Dillon \n \t\t\t\t\t\t\t\t """ 4 => """ B Namjou \n \t\t\t\t\t\t\t\t """ 5 => """ RH Scofield \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1177/0961203309346508" "Revista" => array:7 [ "tituloSerie" => "Lupus" "fecha" => "2010" "volumen" => "19" "numero" => "1" "paginaInicial" => "52" "paginaFinal" => "57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19910391" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1177/0961203309346508" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1177/0961203309346508" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Special Article - The 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ EM Tan \n \t\t\t\t\t\t\t\t """ 1 => """ AS Cohen \n \t\t\t\t\t\t\t\t """ 2 => """ JF Fries \n \t\t\t\t\t\t\t\t """ 3 => """ AT Masi \n \t\t\t\t\t\t\t\t """ 4 => """ DJ McShane \n \t\t\t\t\t\t\t\t """ 5 => """ NF Rothfield \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1002/art.1780251101" "Revista" => array:7 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1982" "volumen" => "25" "numero" => "11" "paginaInicial" => "1271" "paginaFinal" => "1277" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7138600" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1002/art.1780251101" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1002/art.1780251101" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ MC Hochberg \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "1997" "volumen" => "40" "numero" => "9" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1002/art.1780400928" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-time PCR quantification of human complement C4A and C4B genes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ A Szilagyi \n \t\t\t\t\t\t\t\t """ 1 => """ B Blasko \n \t\t\t\t\t\t\t\t """ 2 => """ D Szilassy \n \t\t\t\t\t\t\t\t """ 3 => """ G Fust \n \t\t\t\t\t\t\t\t """ 4 => """ M Sasvari-Szekely \n \t\t\t\t\t\t\t\t """ 5 => """ Z Ronai \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1186/1471-2156-7-1" "Revista" => array:5 [ "tituloSerie" => "BMC Genet" "fecha" => "2006" "volumen" => "7" "paginaInicial" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16403222" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1186/1471-2156-7-1" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1186/1471-2156-7-1" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Which complement assays and typings are necessary for the diagnosis of complement deficiency in patients with lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ P Boeckler \n \t\t\t\t\t\t\t\t """ 1 => """ A Meyer \n \t\t\t\t\t\t\t\t """ 2 => """ B Uring-Lambert \n \t\t\t\t\t\t\t\t """ 3 => """ J Goetz \n \t\t\t\t\t\t\t\t """ 4 => """ B Cribier \n \t\t\t\t\t\t\t\t """ 5 => """ G Hauptmann \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.clim.2006.08.007" "Revista" => array:7 [ "tituloSerie" => "A study of 25 patients. Clin Immunol" "fecha" => "2006" "volumen" => "121" "numero" => "2" "paginaInicial" => "198" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16987709" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.clim.2006.08.007" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.clim.2006.08.007" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Synthesis and Regulation of Complement Components by Human Monocytes macrophages and by acute monocytic leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ F Vincent \n \t\t\t\t\t\t\t\t """ 1 => """ H Delasalle \n \t\t\t\t\t\t\t\t """ 2 => """ A Bohbot \n \t\t\t\t\t\t\t\t """ 3 => """ JP Bergerat \n \t\t\t\t\t\t\t\t """ 4 => """ G Hauptmann \n \t\t\t\t\t\t\t\t """ 5 => """ F Oberling \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1089/dna.1993.12.415" "Revista" => array:7 [ "tituloSerie" => "DNA Cell Biol" "fecha" => "1993" "volumen" => "12" "numero" => "5" "paginaInicial" => "415" "paginaFinal" => "423" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8517928" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1089/dna.1993.12.415" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1089/dna.1993.12.415" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Links between complement abnormalities and systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ MC Pickering \n \t\t\t\t\t\t\t\t """ 1 => """ MJ Walport \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1093/rheumatology/39.2.133" "Revista" => array:7 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2000" "volumen" => "39" "numero" => "2" "paginaInicial" => "133" "paginaFinal" => "141" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10725062" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1093/rheumatology/39.2.133" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1093/rheumatology/39.2.133" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ C Gaboriaud \n \t\t\t\t\t\t\t\t """ 1 => """ J Juanhuix \n \t\t\t\t\t\t\t\t """ 2 => """ A Gruez \n \t\t\t\t\t\t\t\t """ 3 => """ M Lacroix \n \t\t\t\t\t\t\t\t """ 4 => """ C Darnault \n \t\t\t\t\t\t\t\t """ 5 => """ D Pignol \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1074/jbc.M307764200" "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "2003" "volumen" => "278" "numero" => "47" "paginaInicial" => "46974" "paginaFinal" => "46982" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12960167" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1074/jbc.M307764200" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1074/jbc.M307764200" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Structural and functional anatomy of the globular domain of complement protein C1q" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ W Kishore \n \t\t\t\t\t\t\t\t """ 1 => """ R Ghai \n \t\t\t\t\t\t\t\t """ 2 => """ TJ Greenhough \n \t\t\t\t\t\t\t\t """ 3 => """ AK Shrive \n \t\t\t\t\t\t\t\t """ 4 => """ DM Bonifati \n \t\t\t\t\t\t\t\t """ 5 => """ MG Gadjeva \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.imlet.2004.06.015" "Revista" => array:7 [ "tituloSerie" => "Immunol Lett" "fecha" => "2004" "volumen" => "95" "numero" => "2" "paginaInicial" => "113" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15388251" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.imlet.2004.06.015" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.imlet.2004.06.015" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. The complete derived amino acid sequence of human C1q" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ GC Sellar \n \t\t\t\t\t\t\t\t """ 1 => """ DJ Blake \n \t\t\t\t\t\t\t\t """ 2 => """ KBM Reid \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1042/bj2740481" "Revista" => array:7 [ "tituloSerie" => "Biochem J" "fecha" => "1991" "volumen" => "274" "numero" => "Pt 2" "paginaInicial" => "481" "paginaFinal" => "490" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1706597" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonsense and Missense Mutations in the Structural Genes of Complement Component C1q A-Chains and C-Chains are Linked with 2 Different Types of Complete Selective C1q Deficiencies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => """ F Petry \n \t\t\t\t\t\t\t\t """ 1 => """ DT Le \n \t\t\t\t\t\t\t\t """ 2 => """ M Kirschfink \n \t\t\t\t\t\t\t\t """ 3 => """ M Loos \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Immunol" "fecha" => "1995" "volumen" => "155" "numero" => "10" "paginaInicial" => "4734" "paginaFinal" => "4738" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7594474" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple identification of a particular type of hereditary C1q deficiency in the Turkish population: Review of the cases and additional genetic and functional analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ F Petry \n \t\t\t\t\t\t\t\t """ 1 => """ AI Berkel \n \t\t\t\t\t\t\t\t """ 2 => """ M Loos \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1007/s004390050464" "Revista" => array:7 [ "tituloSerie" => "Hum Genet" "fecha" => "1997" "volumen" => "100" "numero" => "1" "paginaInicial" => "51" "paginaFinal" => "56" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9225968" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1007/s004390050464" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1007/s004390050464" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib35" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary C1q deficiency: a new family with C1qA deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ C Sun-Tan \n \t\t\t\t\t\t\t\t """ 1 => """ TT Oezguer \n \t\t\t\t\t\t\t\t """ 2 => """ G Kilinc \n \t\t\t\t\t\t\t\t """ 3 => """ R Topaloglu \n \t\t\t\t\t\t\t\t """ 4 => """ O Gokoz \n \t\t\t\t\t\t\t\t """ 5 => """ S Ersoy-Evans \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Turkish J Pediatr" "fecha" => "2010" "volumen" => "52" "numero" => "2" "paginaInicial" => "184" "paginaFinal" => "186" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib36" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ S Rafiq \n \t\t\t\t\t\t\t\t """ 1 => """ TM Frayling \n \t\t\t\t\t\t\t\t """ 2 => """ TJ Vyse \n \t\t\t\t\t\t\t\t """ 3 => """ DSC Graham \n \t\t\t\t\t\t\t\t """ 4 => """ P Eggleton \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2010.04185.x" "Revista" => array:7 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2010" "volumen" => "161" "numero" => "2" "paginaInicial" => "284" "paginaFinal" => "289" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20528885" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib37" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ B Namjou \n \t\t\t\t\t\t\t\t """ 1 => """ M Keddache \n \t\t\t\t\t\t\t\t """ 2 => """ D Fletcher \n \t\t\t\t\t\t\t\t """ 3 => """ S Dillon \n \t\t\t\t\t\t\t\t """ 4 => """ L Kottyan \n \t\t\t\t\t\t\t\t """ 5 => """ G Wiley \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1177/0961203312443993" "Revista" => array:7 [ "tituloSerie" => "Lupus" "fecha" => "2012" "volumen" => "21" "numero" => "10" "paginaInicial" => "1113" "paginaFinal" => "1118" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22472776" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1177/0961203312443993" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1177/0961203312443993" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib38" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of Clq in patients with subacute cutaneous lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ DM Racila \n \t\t\t\t\t\t\t\t """ 1 => """ CJ Sontheimer \n \t\t\t\t\t\t\t\t """ 2 => """ A Sheffield \n \t\t\t\t\t\t\t\t """ 3 => """ JJ Wisnieski \n \t\t\t\t\t\t\t\t """ 4 => """ E Racila \n \t\t\t\t\t\t\t\t """ 5 => """ RD Sontheimer \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1191/0961203303lu329oa" "Revista" => array:7 [ "tituloSerie" => "Lupus" "fecha" => "2003" "volumen" => "12" "numero" => "2" "paginaInicial" => "124" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12630757" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1191/0961203303lu329oa" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1191/0961203303lu329oa" ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib39" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Listening to silence and understanding nonsense: Exonic mutations that affect splicing" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ L Cartegni \n \t\t\t\t\t\t\t\t """ 1 => """ SL Chew \n \t\t\t\t\t\t\t\t """ 2 => """ AR Krainer \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1038/nrg775" "Revista" => array:7 [ "tituloSerie" => "Nat Rev Genet" "fecha" => "2002" "volumen" => "3" "numero" => "4" "paginaInicial" => "285" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11967553" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1038/nrg775" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1038/nrg775" ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib40" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clq and systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ MJ Walport \n \t\t\t\t\t\t\t\t """ 1 => """ KA Davies \n \t\t\t\t\t\t\t\t """ 2 => """ M Botto \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/S0171-2985(98)80032-6" "Revista" => array:7 [ "tituloSerie" => "Immunobiology" "fecha" => "1998" "volumen" => "199" "numero" => "2" "paginaInicial" => "265" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9777411" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/S0171-2985(98)80032-6" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0171-2985(98)80032-6" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib41" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular, genetic and epidemiologic studies on selective complete C1q deficiency in Turkey" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ AI Berkel \n \t\t\t\t\t\t\t\t """ 1 => """ E Birben \n \t\t\t\t\t\t\t\t """ 2 => """ C Oner \n \t\t\t\t\t\t\t\t """ 3 => """ R Oner \n \t\t\t\t\t\t\t\t """ 4 => """ M Loos \n \t\t\t\t\t\t\t\t """ 5 => """ F Petry \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Immunobiol" "fecha" => "2000" "volumen" => "201" "numero" => "3-4" "paginaInicial" => "347" "paginaFinal" => "355" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S0171-2985(00)80089-3" ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib42" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation by Interferons of the Expression of Monocyte Complement Genes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ DF Lappin \n \t\t\t\t\t\t\t\t """ 1 => """ GD Birnie \n \t\t\t\t\t\t\t\t """ 2 => """ K Whaley \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochem J" "fecha" => "1990" "volumen" => "1" "numero" => "2" "paginaInicial" => "387" "paginaFinal" => "392" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib43" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lupus erythematosus associated with genetically determined deficiency of the second component of the complement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ DM Lipsker \n \t\t\t\t\t\t\t\t """ 1 => """ C Schreckenberg-Gilliot \n \t\t\t\t\t\t\t\t """ 2 => """ B Uring-Lambert \n \t\t\t\t\t\t\t\t """ 3 => """ A Meyer \n \t\t\t\t\t\t\t\t """ 4 => """ D Hartmann \n \t\t\t\t\t\t\t\t """ 5 => """ EM Grosshans \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archderm.136.12.1508" "Revista" => array:7 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2000" "volumen" => "136" "numero" => "12" "paginaInicial" => "1508" "paginaFinal" => "1514" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11115162" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib44" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic, structural and functional diversities of human complement components C4A and C4B and their mouse homologues, Slp and C4" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ CA Blanchong \n \t\t\t\t\t\t\t\t """ 1 => """ EK Chung \n \t\t\t\t\t\t\t\t """ 2 => """ KL Rupert \n \t\t\t\t\t\t\t\t """ 3 => """ Y Yang \n \t\t\t\t\t\t\t\t """ 4 => """ ZY Yang \n \t\t\t\t\t\t\t\t """ 5 => """ B Zhou \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Int Immunoph" "fecha" => "2001" "volumen" => "1" "numero" => "3" "paginaInicial" => "365" "paginaFinal" => "392" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/S1567-5769(01)00019-4" ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib45" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complete deficiencies of complement C4A and C4B including 2-bp insertion in codon 1213 are genetic risk factors of systemic lupus erythematosus in Thai populations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ W Ittiprasert \n \t\t\t\t\t\t\t\t """ 1 => """ S Kantachuvesiri \n \t\t\t\t\t\t\t\t """ 2 => """ K Pavasuthipaisit \n \t\t\t\t\t\t\t\t """ 3 => """ O Verasertniyom \n \t\t\t\t\t\t\t\t """ 4 => """ L Chaomthum \n \t\t\t\t\t\t\t\t """ 5 => """ K Totemchokchyakarn \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.jaut.2005.04.004" "Revista" => array:7 [ "tituloSerie" => "J Autoimmun" "fecha" => "2005" "volumen" => "25" "numero" => "1" "paginaInicial" => "77" "paginaFinal" => "84" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15998580" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.jaut.2005.04.004" "WWW" => array:1 [ "link" => "http://dx.doi.org/10.1016/j.jaut.2005.04.004" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack639329" "titulo" => "ACKNOWLEDGMENTS" "texto" => "<p id="para240" class="elsevierStylePara elsevierViewall">The authors gratefully acknowledge all of the patients for their kind participation. The authors also acknowledge Luis EC Andrade and Estela M Novak for their assistance with laboratory tests and mRNA expression data analysis.</p><p id="para250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Financial support:</span> This study was supported by São Paulo Research Foundation (FAPESP) grant 2008/58238-4.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/0000007000000003/v1_202212011445/S1807593222014156/v1_202212011445/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/0000007000000003/v1_202212011445/S1807593222014156/v1_202212011445/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222014156?idApp=UINPBA00004N" ]
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