COMMON VARIABLE IMMUNODEFICIENCY - CLINICAL ASPECTS AND RECENT PROGRESS IN IDENTIFYING THE IMMUNOLOGICAL DEFECT(S)

Common variable immunodeficiency (CVID) comprises a heterogeneous grou p of patients with as yet undefined genetic defects. Patients with CVI D have in common a decrease in the levels of one or more serum immunog lobulin isotypes and a severe defect in the production of specific ant ibodies. Typically, the patients suffer from recurrent infections of t he upper and lower respiratory tract or the gastrointestinal tract. In consequence of these infections patients may develop severe organ dam age, such as chronic pulmonary disease with bronchiectases, leading to pulmonary failure. Early diagnosis of CVID is important, as antibody deficiency can efficiently be treated by regular intravenous IgG (IVIG ) substitution therapy. IVIG therapy prevents the occurrence of. furth er acute infectious episodes and the development of long-term complica tions. The basic immunological defect(s) in patients with CVID are sti ll unknown. There is currently no convincing evidence for an intrinsic B-cell defect in patients with CVID. A defect in T-cell activation du e to impaired signal transduction upon T-cell receptor triggering has been described in a large subgroup of patients with CVID. Defective T- cell activation may lead to an impairment in cognate T-B-cell interact ion due to impaired expression of CD40 ligand and/or abnormalities in the production T-cell-derived cytokines required for fully functional B-cell activation, proliferation and/or differentiation which could in deed explain the impairment in antibody production present in CVID pat ients.