PRIMARY IMMUNODEFICIENCY DISORDERS - PATHOGENESIS AND TREATMENT

Primary or congenital immunodeficiency disorders are caused by genetic defects in the immune system. The principal consequence of immunodefi ciency is an increased susceptibility to recurrent infections and/or i nfections with otherwise nonpathogenic micro-organisms; this may be pr eceded and/or accompanied by symptoms suggesting an impairment of immu ne regulation, such as autoimmune reactivity, allergy, joint disease a nd malignancies. Increased susceptibility to infection may result from abnormalities in nonspecific host defense mechanisms, for example com plement deficiencies and phagocyte defects, or from defects in the dev elopment and function of the T and B cell lineages of the immune syste m, affecting specific immunity. Deficient antibody production is the p redominant abnormality in the majority of primary immunodeficiency dis orders, while patients with combined immunodeficiencies show defects i n both the T and B cell systems. Primary disorders of specific immunit y can be due to: (a) developmental defects, leading to the absence of immunocompetent T or B cells, such as in X-linked severe combined immu nodeficiency or X-linked agammaglobulinaemia; (b) metabolic abnormalit ies affecting the immune system, such as in adenosine deaminase defici ency; (c) defective expression or function of cell membrane molecules involved in cell-cell interaction, such as major histocompatibility co mplex (MHC) class II deficiency; or (d) defects in T cell function in the presence of normal numbers of peripheral T cells, such as in CD3 d eficiency or ZAP-70 deficiency. Transplantation of bone marrow cells f rom human leucocyte antigen (HLA)identical or genotypically HLA-compat ible family members often results in complete immunological reconstitu tion in patients with severe combined immunodeficiency. Immunoglobulin replacement is indicated in all patients with significantly diminishe d IgG levels and/or in those with severe impairment of antibody produc tion. Clinical experience with intravenous immunoglobulin has shown th at this treatment can be life-saving if it is started early and if suf ficient amounts are given with sufficient frequency.