Leucocyte adhesion deficiency type 1 (LAD-1) is a rare autosomal recessive primary immunodeficiency disorder, characterised by the absence or deficient expression of the adhesion molecules on leucocytes. The disease is usually associated with leucocytosis, recurrent severe bacterial and fungal infections without pus formation and impaired wound healing. Omphalitis, delayed umbilical cord separation, perirectal abscess, sepsis, necrotising enterocolitis, pneumonia, gingivitis and periodontitis are common features of disease.1–3 Although some forms of primary immunodeficiency diseases could develop malignancies, there is no report of non-Hodgkin's lymphoma in patients with LAD.
Herein a boy is presented who was admitted to the NICU ward because of omphalitis, sepsis, icterus and erythematus rashes. He was the second child of consanguineous parents. The first child of the family was a girl who died at three months of age due to pneumonia. The culture of umbilical discharge of the patient was Pseudomonas spp. While he was receiving treatment, he developed right foot cellulites. Radioisotope scanning showed arthritis in right knee. His umbilical cord had been cut on 32 days of life. Lab data revealed leucocytosis 30,000/mm3 with neutrophilia (65%) and eosinophilia (10%). Serum immunoglobulin (Ig)G, IgM, IgA, and NBT tests were all normal. Peripheral blood flow cytometric analysis revealed normal T-, B- and NK cell numbers, but was compatible with LAD-1 (CD18=0.5%, CD11a=0.5%, CD11b=0%, CD11c=1.2%). He had history of several episodes of sepsis, pneumonia, diarrhoea, typhlitis, necrotic skin ulcers and infections because of Pseudomonas spp. and S. aureus after diagnosis.
The 3rd sibling of this family is a girl, who was admitted to the NICU at age of 30 days because of delayed separation of umbilical cord and omphalitis. Her laboratory data revealed leucocytosis (27,000/mm3) with neutrophilia (82%). Serum immunoglobulins and NBT were normal. Chemotaxis was impaired and peripheral blood flow cytometric analysis revealed low expression of CD18 (CD18=1.6%, CD11a=0.2%, CD11b=1.0%, CD11c=5%). T-, B- and NK subpopulation numbers were normal. Now, she is six years old and has undergone recurrent severe diarrhoea, pneumonia, skin infections with necrotic ulcers due to Pseudomonas spp. and S. aureus, chronic gingivitis and chronic otitis media with discharge. Both siblings have failure to thrive.
During follow-up, the boy was admitted into the hospital due to abdominal mass at the age of seven years. The mass (3cm×4cm) removed in appendix with partial residue in ileocecal region during laparotomy. Pathology reported diffuse large B-cell lymphoma as a primary tumour in the abdomen being positive for CD20 and CD22. Genetic evaluation showed t (8:14) in mass. Other investigation to determine the clinical extent of the disease for staging showed stage II of disease. He received LMB-96 protocol. During chemotherapy, he had several episodes of severe infection and abscess formation. The result of treatment was excellent after treatment and now he is alive, 11 years old, without any recurrence of disease.
Several manifestations have been reported in LAD patients, the severity of which appears to be related to the degree of surface expression of CD18 and CD11. However, to the best of our knowledge, NHL has not been reported in LAD. However, unfortunately, the lymphoma itself was not tested for CD11 or CD18. NHL, which is malignant proliferation of lymphocytes, seems to be one of the most common childhood malignancies. As genetic abnormalities are risk factors for NHL, such abnormalities in integrin molecules could predispose patients to malignancy in lower ages. As β2 integrins are essential for the regulation of antigen-dependent activation threshold, low expression of the molecule could cause deficiency in the quantitative and qualitative of CD4+ T-cells and lymphocytes that normally regulate immune function and suppress malignant clone. There is some evidence showing association of primary immunodeficiency disorders and cancers.4 Although predisposition to viral infections as well as susceptibility to DNA breakage were considered as specific aetiologies of a number of cancers in certain immunodeficiencies, the exact biological pathway and mechanisms for such association have not been completely recognised. Development of malignancy in LAD patients could provide insight into the possible role of β2 integrins in cancers.
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