X-linked hyper-IgM syndrome (CD40 ligand deficiency). Patients in the Czech Republic and literature review

Abstract

Hyper-IgM syndrome (HIGM) is a group of rare and serious primary immunodeficiencies. It is characterised by very low levels of IgG, IgA and IgE immunoglobulins whereas the level of IgM is normal or elevated. It is caused by impairment of immunoglobulin isotype switching. Either the signalling pathway of CD40 molecule, intrinsic B-cell signalling or DNA reparation mechanism are defective. The most frequent defect lies in the gene coding for CD40 ligand (X-linked Hyper-IgM syndrome). Apart from humoral immunity also the T-cell function is affected. Thus, the patients suffer from infections caused by opportunistic pathogens (most frequently Pneumocystic jirovecii, CMV, Cryptococci, Mycobacteria). Recurrent respiratory tract infections are frequently seen. Chronic diarrhoea may be present as well and may associate with failure to thrive. More than a half of the patients suffer from chronic neutropenia. Arthritis, thrombocytopenia, haemolytic anaemia and nephritis are documented in some patients. Patients with CD40 ligand deficiency have increased risk of malignant diseases. The cornerstones of the therapy are preventive measures, antibiotic prophylaxis and immunoglobulin substitution. The haematopoietic stem cell transplantation is the only curative therapy currently available. Between 1993 and 2011 there were 5 patients with CD40 ligand deficiency diagnosed and treated in the Czech Republic. Three patients were indicated for haematopoietic stem cell transplantation. The authors present an overview of the disease's course, diagnostic process and treatment of these patients.