IMMUNE-RESPONSES TO 18.6-KDA AND 30-KDA MYCOBACTERIAL ANTIGENS IN RHEUMATOID PATIENTS, AND V-BETA USAGE BY SPECIFIC SYNOVIAL T-CELL LINES AND FRESH T-CELLS

We have investigated both the humoral and the cellular immune responses of patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA) to mycobacterial antigens. The JRA group was not Bacillus Calmette Guerin (BCG) vaccinated whilst the majority of the RA group was. As determined by immunoblotting, 79% of sera from patients with JRA reacted mainly with a 18.6-kDa protein (P18.6), whilst 70% of sera from patients with RA reacted mainly with a 30-kDa protein (P30) of BCG, M. tuberculosis and M. kansasii. In contrast, only a moderate proportion of the control sera (25% of adult and 20% of children) showed reactivity to P30, and none of the samples had significant reactivity with the P,8.6 antigen. Furthermore, T-cell proliferation to the P18.6 and P30 antigens was detected in the majority of JRA and RA patients, and was nearly always higher in synovial fluid (SF) than in the peripheral blood (PB). We also investigated the usage of V-beta family genes in P18.6 and P3, antigen-specific T-cell lines established from the SF of one patient with active PA. We showed that V-beta-2,-4,-5,-6,-7,-14,-17,-18 and V-beta-19 were over-represented compared with other known V-beta families. We also noted that the proportion Of V-beta-14 was higher in freshly isolated SF mononuclear cells compared with the blood in this patient and in 2 out of 4 other RA patients examined. Other V-beta families such as V-beta-6, V-beta-8, V-beta-16, V-beta-18 and V-beta-19 were also over-represented in the SF compared with the blood in some patients. Taken together our results provide more information concerning the role of mycobacterial antigens in RA and suggest that there may be an in vivo clonal expansion of T lymphocytes in the synovium.