SHARED AMINO-ACID-SEQUENCES BETWEEN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GLYCOPROTEINS, TYPE-XI COLLAGEN AND PROTEUS-MIRABILIS IN RHEUMATOID-ARTHRITIS

Objectives-To show molecular similarity between two sequences of Prote us mirabilis (haemolysin-ESRRAL; urease-IRRET) with HLA-DR antigens (E QRRAA) which are associated with rheumatoid arthritis (RA) and type XI collagen (LRREI), respectively; and, in patients with RA, to measure levels of antibody against a 16-mer synthetic peptide containing the E SRRAL sequence, and the haemolysin and urease proteins of Proteus mira bilis. Methods-The homologous sequences EQRRAA and ESRRAL were modelle d with Alchemy III, using the crystalline structure of DRB10101 (HLA- DR1). Sera from 40 patients with RA, 30 with ankylosing spondylitis (A S), and 30 controls were tested against synthetic ESRRAL peptide and t he haemolysin of Proteus mirabilis by enzyme linked immunosorbent assa y. Similar tests were also carried out on sera from 20 patients with R A, 40 with AS, and 15 controls, against Proteus mirabilis urease. Resu lts-Molecular modelling of the homologous sequences ESRRAL/EQRRAA and IRRET/LRREI showed stereochemical similarities. Antibodies to the 16-m er synthetic peptide containing the ESRRAL sequence, the haemolysin, a nd urease proteins were significantly increased in RA patients compare d with AS patients (p < 0.001) and healthy controls (p < 0.001). No wi th the EDERAA sequence of DRB10402 (HLA-DR4Dw10), the haemolysin prot eins of Streptococcus pyogenes and Vibrio parahaemolyticus, and the ur ease of Bacillus pasteurii. Conclusion-The additive effect of the immu ne responses to the two Proteus mirabilis antigens, haemolysin (ESRRAL ) and urease (IRRET), could be relevant in the aetiopathogenesis of RA .