Genetic markers of rheumatoid arthritis in a Western Cape black and coloured population

Abstract

Intensive investigations in many different populations over the last decade, have indicated a failure to understand the inheritance of rheumatoid arthritis (RA). It was hoped that genes within the class IT region of the major histocompatibility complex (MHq could shed some light on the inheritance of this autoimmune disease and which are now known without doubt, to confer susceptibility to the disease. Genetic studies of RA have concentrated primarily on its autoimmune nature and several investigations of MHC class IT molecules, have demonstrated an association between specific HIA alleles and susceptibility to RA, in particular the DRBI*04 and DRBI*01 alleles. - The HIA system is known to be associated with many diseases involving an immune aetiology. The structural features of specific DR and DQ genes give clues to the molecular mechanisms by which these alleles are associated with RA It has been found by many investigators that there is more than one susceptibility allele for RA at the DRBI locus. Questions arise whether the DRBI molecule itself directly contributes to the pathogenesis ofRA and why some DRBI genes carrying DRBI*04 alleles, are not associated withRA Animal studies have emphasised the critical importance of T-cells in the pathogenesis of RA Immune responsiveness is thought to be controlled by specific allelic variation by determining the ability of specific T-cell receptors (fCRs) to be triggered by recognition of class IT molecules during the induction of the immune response. In a disease such as RA, however, where multiple alleles are thought to confer risk, it is not yet known whether each of these alleles shares some common structural feature triggering a single T-cell pathway or whether each allele represents an alternative recognition site which triggers different T-cell clones, all of which lead to a similar clinical syndrome.