Genetic Determination and Immunopathogenesis of Systemic LupusErythematosus

Overview

Systemic lupus erythematosus (SLE) belongs to organ non-specific autoimmunedisorders. Similarlyto other autoimmune diseases, SLE is also genetically determined. Among many genes involved inthe predisposition to SLE those of the major histocompatibility complex (HLA) and the complementsystem (C2, C4, C1q, and MBP) have already been known for many years. Recently new genes wereadded to this list – the FcγRIIA gene (the receptor for Fc-fragment of IgG), the Fas and FasL genesinvolved in the regulation of apoptosis, and the TNF (tumour necrosis factor) gene. Hormones,especially oestrogens, substantially contribute to the pathogenesis of the disease as they stimulatelymphocytes to produce cytokines (IL-4, IL-6, IL-10) supporting antibody production by B-lymphocytes;moreover they suppress cellular immunity. SLE is a prototypic disease in which antibodiesare responsible directly or indirectly, via immunocomplexes, for clinical symptoms. B cells areactivated, thenumberofCD4+-lymphocytes is decreasedcompared todouble negativeT-lymphocytes(CD4-CD8-), the number of which is increased. Changes in the cytokine network are also observed,esp. increased levels of IFN-α, IL-4, IL-6, IL-2 receptor, and adhesive molecule ICAM-1 have beenreported.

Key words:
autoantibodies, cytokines,HLA-complex,hormones,immunocomplexes, lymphocytesT and B