Clinical significance of immunogenetic studies in rheumatic diseases

The genetic predisposition to different autoimmune rheumatic diseases among Bulgarian population associated with HLA-A, B, DR, DQ, DP antigens was examined. We have performed systemic studies to find an associations and to evaluate their clinical importance. We have analyzed the results of HLA typing of patients with inflammatory rheumatic diseases (2224), JAC (36), ReA (201), PsA (130), RA (151), JCA (148), SLE (114), pSS (50), inflammatory eye diseases (230) and healthy controls (1525). All of the autoimmune rheumatic diseases in Bulgarians show associations with three types predisposing antigen constellations: 1) HLA-B27 and/or HLA-B7-CREG-in Spondylarthropathies (AC, JAC, ReA, PsA, eye diseases-anterior eye segment and undifferentiated oligoarthropathy); 2) HLA-DR4-in RA, ReA, PsA, JCA; 3) HLA-A1,B8,DR3,DQ2 or haplotype A1-B8-DR3-DQ2-in SLE, pSS and combination with other autoimmune diseases, especially thyroid pathology. Correlation of HLA-B27 with arthralgia, acute rheumatism, gout, RA and other connective tissue disorders have not been found. We consider that HLA-DR4 is a genetic marker for arthritis in general, not only for RA. Patients with RA who are DRB1*0404 (+) positive and these heterozygous of DRB1*0401/DRB1*0404 possess high RR to develop severe RA. The established HLA associations with rheumatic diseases are specific for the Bulgarian population, although they are equally or similar to typical European populations. On the basis of founded HLA associations we have proposed a new classification of autoimmune rheumatic diseases and we have provided useful information about their genetic heterogeneity and clinical importance for diagnosis, prognosis and prophylaxis of diseases.