Letter to the Editor
Immunomodulation for Pompe Disease with high sustained antibodies against enzyme replacement therapy
Inmunomodulación con altos títulos mantenidos de anticuerpos contra terapia de reemplazo enzimático en la enfermedad de Pompe
Javier Blasco-Alonsoa,b,
, Raquel Gil-Gómezc, Alfonso Lendínez Juradoa, Raquel Yahyaoui Macíasd
Corresponding author
a UGC Pediatría. Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain
b Grupo IBIMA Multidisciplinar de Investigación Pediátrica, Universidad de Málaga, Spain
c Unidad de Gestión Clínica de Cuidados Críticos y Urgencias de Pediatría, Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain
d Unidad de Gestión Clínica Laboratorio, Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain
Read
9
Timeswas read the article
3
Total PDF
6
Total HTML
Share statistics
array:24 [ "pii" => "S0025775320307557" "issn" => "00257753" "doi" => "10.1016/j.medcli.2020.09.017" "estado" => "S300" "fechaPublicacion" => "2021-10-22" "aid" => "5473" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;157:403-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "en" => array:19 [ "pii" => "S2387020621005210" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.09.015" "estado" => "S300" "fechaPublicacion" => "2021-10-22" "aid" => "5473" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;157:403-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Immunomodulation for Pompe Disease with high sustained antibodies against enzyme replacement therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "403" "paginaFinal" => "405" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inmunomodulación con altos títulos mantenidos de anticuerpos contra terapia de reemplazo enzimático en la enfermedad de Pompe" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3028 "Ancho" => 2167 "Tamanyo" => 376924 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Measurement of left ventricular index, Glc4 levels and Anti-rhGAA antibody titers in different moments before and after administration of immunomodulatory agents.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Javier Blasco-Alonso, Raquel Gil-Gómez, Alfonso Lendínez Jurado, Raquel Yahyaoui Macías" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Javier" "apellidos" => "Blasco-Alonso" ] 1 => array:2 [ "nombre" => "Raquel" "apellidos" => "Gil-Gómez" ] 2 => array:2 [ "nombre" => "Alfonso Lendínez" "apellidos" => "Jurado" ] 3 => array:2 [ "nombre" => "Raquel Yahyaoui" "apellidos" => "Macías" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0025775320307557" "doi" => "10.1016/j.medcli.2020.09.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320307557?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621005210?idApp=UINPBA00004N" "url" => "/23870206/0000015700000008/v1_202110160801/S2387020621005210/v1_202110160801/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S0025775320307533" "issn" => "00257753" "doi" => "10.1016/j.medcli.2020.09.015" "estado" => "S300" "fechaPublicacion" => "2021-10-22" "aid" => "5471" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;157:405-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Major orthopedic surgery in a patient with fibromuscular dysplasia in the right renal artery and mild hemophilia A: First case reported" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "405" "paginaFinal" => "406" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Paciente con displasia fibromuscular en arteria renal derecha y hemofilia A leve intervenido de cirugía ortopédica mayor: primer caso reportado" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mariana Fernández Caballero, Fernando Collado, José-Tomás Navarro" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Mariana" "apellidos" => "Fernández Caballero" ] 1 => array:2 [ "nombre" => "Fernando" "apellidos" => "Collado" ] 2 => array:2 [ "nombre" => "José-Tomás" "apellidos" => "Navarro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020621005209" "doi" => "10.1016/j.medcle.2020.09.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621005209?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320307533?idApp=UINPBA00004N" "url" => "/00257753/0000015700000008/v1_202110170505/S0025775320307533/v1_202110170505/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S0025775320307259" "issn" => "00257753" "doi" => "10.1016/j.medcli.2020.09.004" "estado" => "S300" "fechaPublicacion" => "2021-10-22" "aid" => "5443" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2021;157:402-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Encefalopatía hiperamoniémica en una paciente con telangiectasia hemorrágica hereditaria" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "402" "paginaFinal" => "403" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hyperammonemic encephalopathy in a patient with hereditary hemorrhagic telangiectasia" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joana de Miguel Landiríbar, Oihane Orokieta Rincón, Alfonso Gutiérrez Macías" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Joana" "apellidos" => "de Miguel Landiríbar" ] 1 => array:2 [ "nombre" => "Oihane" "apellidos" => "Orokieta Rincón" ] 2 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Gutiérrez Macías" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020621005064" "doi" => "10.1016/j.medcle.2020.09.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621005064?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320307259?idApp=UINPBA00004N" "url" => "/00257753/0000015700000008/v1_202110170505/S0025775320307259/v1_202110170505/es/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Immunomodulation for Pompe Disease with high sustained antibodies against enzyme replacement therapy" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "403" "paginaFinal" => "405" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Javier Blasco-Alonso, Raquel Gil-Gómez, Alfonso Lendínez Jurado, Raquel Yahyaoui Macías" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Javier" "apellidos" => "Blasco-Alonso" "email" => array:1 [ 0 => "javierblascoalonso@yahoo.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Raquel" "apellidos" => "Gil-Gómez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Alfonso Lendínez" "apellidos" => "Jurado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Raquel Yahyaoui" "apellidos" => "Macías" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "UGC Pediatría. Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Grupo IBIMA Multidisciplinar de Investigación Pediátrica, Universidad de Málaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Gestión Clínica de Cuidados Críticos y Urgencias de Pediatría, Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Gestión Clínica Laboratorio, Hospital Materno-Infantil, Hospital Regional Universitario de Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inmunomodulación con altos títulos mantenidos de anticuerpos contra terapia de reemplazo enzimático en la enfermedad de Pompe" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3028 "Ancho" => 2167 "Tamanyo" => 376924 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Measurement of left ventricular index, Glc4 levels and Anti-rhGAA antibody titers in different moments before and after administration of immunomodulatory agents.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Enzyme replacement therapies (ERT) have prolonged the survival and improved clinical outcomes of patients suffering from a multitude of disorders. Some of the Infantile Pompe Disease (IPD) patients treated with alglucosidase alfa develop anti-rhGAA IgG antibodies<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> and the longer term therapeutic efficacy of alglucosidase alfa appears to be more strongly associated with them. Several investigators have unsuccessfully made attempts<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2–5</span></a> in IPD treated with therapeutic proteins to either achieve immune tolerance or mitigate the immune response, including increasing the dose of therapeutic protein and implementing various drug regimens.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Here, we report the first successful achievement in Spain of true immune tolerance to ongoing ERT in a IPD girl with high sustained antibody titles (HSAT).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patient is a Chinese descent girl who presented at age 15 days with normal motor development and a cardiac murmur; echocardiogram showed significant biventricular hypertrophy. She was diagnosed with IPD at age 1 month and ERT was started at 20<span class="elsevierStyleHsp" style=""></span>mg/kg biweekly. Later on, she was cataloged as CRIM-negative IPD at age 4 months. Initial Glc4 levels were 21.8<span class="elsevierStyleHsp" style=""></span>mmol/mol creatinin at age 1 month.</p><p id="par0020" class="elsevierStylePara elsevierViewall">She initially benefited clinically from ERT, as evidenced by reduction in left ventricular mass index (LVMI) from 107<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> to 94<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> at 6 months of age) and maintaining normal Gross Motor Function (level 1). She maintained adequate physical activity and progressed in developmental motor milestones; an initial phase of improvement in LVMI (100<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span>, 20 months, to 62.3<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span>, 24 months) was also noted. At 24 months of age, she first developed HSAT (1/700) and began generalized hypotonia, tongue protrusion, facial myopathy, and cardiomegaly (LVMI values deteriorated from 62.3<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> at 24 months of age, to 139<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> at 30 months and 200.9<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> at 36 months); however, she did not need any respiratory support and tolerated normal oral feeds and was growing normally (62 percentile of weight and height at 33 percentile). For several weeks, ERT was increased from 20 to 35<span class="elsevierStyleHsp" style=""></span>mg/kg/dose with no difference in clinical or functional evaluation. Her antibody titers continued to rise, peaking at 1/1600 at 36 months of age, accompanied by increased urinary Glc4 levels (19.4<span class="elsevierStyleHsp" style=""></span>mmol/mol creatinine at 6 months, to 21.5<span class="elsevierStyleHsp" style=""></span>mmol/mol creatinine at 3 years). At age 41 months, she was hospitalized in the intensive care unit because of an upper respiratory tract infection, and she became ventilator dependent for 2 months and required nasogastric tube feeds. After improvement from acute phase and ventilation withdrawal she was discharged with a Gross Motor Function classification system at level 3 and an increase in antibody titers up to 1/32,000.</p><p id="par0025" class="elsevierStylePara elsevierViewall">An ITI protocol was initiated at 49 months of age (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), with intravenous rituximab (4 doses) and subcutaneous methotrexate (9 doses) for 6 weeks and monthly immunoglobulin infusion for 5 months, resulting in a reduction in titers (1/800 after 6 weeks of treatment, 1/200 after 32 weeks, 1/100 after 112 weeks) and an improvement in gross motor function indexes (level 2), although maintaining facial amymia and easy tiredness in school activities. Urinary Glc4 levels were 20<span class="elsevierStyleHsp" style=""></span>mmol/mol creatinine and LVMI was 104<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> at 24 weeks after the end of ITI. ERT continued to be successfully administered afterwards.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Although the ITI treatment described here prolongs survival and improves significant overall clinical outcomes, closer examination clearly demonstrates residual muscle weakness and gross motor function below age-appropriate levels along with feeding difficulties.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We believe our immune-modulating strategy has potentially broader clinical implications. Use of the protocol described herein is designed to take place over a relatively brief period of time. This protocol has helped lower antibody titers in these ill IPD patient; however, there is still a need for development of a less extensive protocol with agents that are antigen specific to reduce the immune response. Additional research will be needed to establish the proper dosing regimen of immune-suppressive agents in Pompe and other conditions and the optimal way to taper the maintenance regimen following rituximab and/or other immunomodulatory agent treatments to ensure long-lasting tolerance. Our protocol was well tolerated, safe, and effective in reducing a life-threatening immune response and was successful in inducing long-term immune tolerance.<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3028 "Ancho" => 2167 "Tamanyo" => 376924 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Measurement of left ventricular index, Glc4 levels and Anti-rhGAA antibody titers in different moments before and after administration of immunomodulatory agents.</p>" ] ] 1 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">What's already known on this feature?</span><p id="par0040" class="elsevierStylePara elsevierViewall">Several immune tolerance regimes have been described but always in very few patients, none of them in Spain to the best of our knowledge.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">What's new on this feature?</span><p id="par0045" class="elsevierStylePara elsevierViewall">Although clinical experience and current literature on the use of ITI protocols are greatly limited, success is more likely when immune modulation is previously demonstrated.</p></span></span>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical guidelines for infantile-onset Pompe disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.I. Pascual-Pascual" 1 => "A. Nascimento" 2 => "C.M. Fernandez-Llamazares" 3 => "C. Medrano-Lopez" 4 => "E. Villalobos-Pinto" 5 => "M. Martinez-Moreno" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Neurol" "fecha" => "2016" "volumen" => "63" "paginaInicial" => "269" "paginaFinal" => "279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27600742" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune modulation in Pompe disease treated with enzyme replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.G. Banugaria" 1 => "T.T. Patel" 2 => "P.S. Kishnani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/eci.12.40" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Clin Immunol" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "497" "paginaFinal" => "499" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22992140" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y.H. Messinger" 1 => "N.J. Mendelsohn" 2 => "W. Rhead" 3 => "D. Dimmock" 4 => "E. Hershkovitz" 5 => "M. Champion" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/gim.2011.4" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2012" "volumen" => "14" "paginaInicial" => "135" "paginaFinal" => "142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22237443" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "B-Cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.E. Elder" 1 => "S. Nayak" 2 => "S.W. Collins" 3 => "L.A. Lawson" 4 => "J.S. Kelley" 5 => "R.W. Herzog" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jpeds.2013.06.055" "Revista" => array:4 [ "tituloSerie" => "J Pediatr" "fecha" => "2013" "volumen" => "163" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23958115" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.G. Banugaria" 1 => "S.N. Prater" 2 => "J.K. McGann" 3 => "J.D. Feldman" 4 => "J.A. Tannenbaum" 5 => "C. Bailey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/gim.2012.110" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "123" "paginaFinal" => "131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23060045" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00257753/0000015700000008/v1_202110170505/S0025775320307557/v1_202110170505/en/main.assets" "Apartado" => array:4 [ "identificador" => "66430" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas al Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00257753/0000015700000008/v1_202110170505/S0025775320307557/v1_202110170505/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775320307557?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 March | 2 | 0 | 2 |
| 2023 February | 1 | 0 | 1 |
| 2021 November | 1 | 3 | 4 |
| 2021 October | 2 | 0 | 2 |
