title: Antimycobacterial hsp65 and rheumatoid factor titres in a population of normal twins: evidence of genetic control of rheumatoid factor.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease and rheumatoid factor (RF), anti-IgG, has been implicated in the pathogenesis, but the exact etiology remains unclear. There are data to suggest and infectious trigger to the autoimmune process, and mycobacteria are considered a candidate. Immunization of various animals with mycobacterial heat shock 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 isolated from inflamed synovium. Mycobacterial hsp65 has also been implicated in other autoimmune disease and in atherosclerosis. The anti-mhsp65 and RF (IgG, IgM and IgA isotypes) titres were assayed by ELISA in 123 pairs of normal twins (61 monozygotic and 62 dizygotic, age 14-79 years), to examine the population distribution and inter-relationship of these antibodies. In addition, we studied the effects of age, sex, genetics and environment on antibody titres. IgG-RF and IgM-RF were detectable in all subjects and IgA-RF in 41 subjects. None of the RF isotypes showed any significant dependence on age or sex. There was a statistically 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 indicates that there is a genetic influence on RF titres. Anti-mhsp65 titres 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 influences on anti-mhsp65 titres are very small, with no evidence of any genetic influence at all. There was no significant relationship of anti-mhsp65 titre with age, sex or RF titres.
authors.affiliation: Department of Medicine and Therapeutics, University of Glasgow, Gardiner Institute, UK.
authors.forename: D
authors.initials: D
authors.lastname: Birnie
authors.forename: I C
authors.initials: IC
authors.lastname: McKay
authors.forename: J
authors.initials: J
authors.lastname: Veitch
authors.forename: K
authors.initials: K
authors.lastname: Whaley
authors.forename: S
authors.initials: S
authors.lastname: Hood
authors.forename: W S
authors.initials: WS
authors.lastname: Hillis
authors.forename: E R
authors.initials: ER
authors.lastname: Holme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood* / Q000235:genetics / Q000276:immunology; D014427:Twins
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C074119:heat-shock protein 65, Mycobacterium; D012217:Rheumatoid Factor; D018833:Chaperonins