ANTIMYCOBACTERIAL HSP65 AND RHEUMATOID-FACTOR TITERS IN A POPULATION OF NORMAL TWINS - EVIDENCE OF GENETIC-CONTROL OF RHEUMATOID-FACTOR

Rheumatoid arthritis (RA) is an autoimmune disease and rheumatoid fact or (RF), anti-IgG, has been implicated in the pathogenesis, but the ex act etiology remains unclear. There are data to suggest an infectious trigger to the autoimmune process, and mycobacteria are considered a c andidate. Immunization of various animals with mycobacterial heat shoc k protein 65 (mhsp65) protects against subsequent autoimmune arthritis in a number of experimental models. Elevated anti-mhsp65 titres have been demonstrated in RA patients, together with specific T cells isola ted from inflamed synovium. Mycobacterial hsp65 has also been implicat ed in other autoimmune disease and in atherosclerosis. The anti-mhsp65 and RF (IgG, IgM and IgA isotypes) titres were assayed by ELISA in 12 3 pairs of normal twins (61 monozygotic and 62 dizygotic, age 14-79 ye ars), to examine the population distribution and inter-relationship of these antibodies. In addition, we studied the effects of age, sex, ge netics and environment on antibody titres. IgG-RF and IgM-RF were dete ctable in all subjects and IgA-RF in 41 subjects. None of the RF isoty pes showed any significant dependence on age or sex. There was a stati stically significant correlation between twins for the IgG-RF and IgM- RF, and a positive but not significant correlation for the IgA-RF. All three correlations were stronger for monozygotic than dizygotic twins , reaching statistical significance for IgM-RF (P < 0.001), and this i ndicates that there is a genetic influence on RF titres. Anti-mhsp65 t itres were detectable in 90.5% of the study group with a range of 0.15 -19.7 AU/ml. There were weak correlations between twins, stronger for dizygotic than monozygotic twins. This suggests that familial influenc es on anti-mhsp65 titres are very small, with no evidence of any genet ic influence at all. There was no significant relationship of anti-mhs p65 titre with age, sex or RF titres.