ABSTRACT
The autoimmune rheumatic diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogrens’ syndrome. The aetiology of these diseases is multifactorial but each has a significant genetic component and, in common with other autoimmune diseases, a significant proportion arises from the major histocompatibility complex (MHC) at 6p21.3. Rheumatoid arthritis for example has a genetic contribution of 30-50% with around one-third arising from the MHC. Most studies have implicated a group of alleles encoding a similar amino acid sequence in the peptide binding groove of DRB1 termed the shared epitope (SE). Furthermore, severity is associated with SE genotypes with DRB1*0401 homozygosity increasing the risk of developing aggressive, systemic disease. The overall genetic contribution to SLE is stronger than that for RA (s 20 and 8, respectively) and includes a complex MHC contribution involving the complement cluster, DRB1 and the telomeric class III region. Recently progress has been made in mapping non-MHC susceptibility genes with a non-synonomous SNP in the gene encoding a protein tyrosine phosphatase (PTPN22) protein tyrosine phosphatase being implicated in susceptibility to both SLE and RA.1,2
Rheumatoid arthritis is a heterogeneous complex inflammatory disorder with a prevalence of approximately 1%. It primarily affects synovial joints but is a systemic disease frequently manifesting extra-articular features. The characteristic pathology in RA is increased thickness of the synovial lining layer containing macrophages and fibroblast-like synoviocytes, while the sub-lining infiltration is composed of inflammatory cells including T and B cells and macrophages, blood vessels and fibroblasts. A complex interplay of inflammatory mediators including cytokines and chemokines have been implicated in the development and maintenance of the chronic inflammation and tissue destruction typical of RA.
