Rheumatoid arthritis: how well do the theories fit the evidence?

• Published in: Clinical and experimental immunology Vol. 92; no. 1; pp. 1 - 6
• Main Authors: McCULLOCH, J., LYDYARD, P. M., ROOK, G. A. W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-1993; Blackwell
• Subjects: Arthritis, Rheumatoid - etiology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoimmunity; Bacterial Infections - complications; Biological and medical sciences; Diseases of the osteoarticular system; Humans; Hypothalamo-Hypophyseal System - physiology; immunogenetics; Inflammatory joint diseases; Intestines - microbiology; Medical sciences; Pituitary-Adrenal System - physiology; rheumatoid arthritis; slow bacterial infection; Human; Immunopathology; HLA-System; T cell receptor; Acute; Diseases of the osteoarticular system; Beta-Peptide chain; Inheritance; Etiopathogenesis; Inflammatory joint disease; Review; Immunogenetics; Rheumatoid arthritis; T-Lymphocyte
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.1993.tb05938.x

SUMMARY
In this brief review, inspired partly by a symposium at the autumn meeting of the British Society for Immunology, 1992, varying hypotheses concerning the etiopathogenesis of rheumatoid arthritis (RA) are explored and tested against current evidence. Immunogenetic considerations, whilst of interest, have not aided our understanding of the development of this disease. The association with restricted HLA‐DR β chain hypervariable sequences does not hold true with all cases of RA (but may be related to disease severity) and studies of T cell receptor (TCR) β chain usage fail to show consistent oligoclonality of infiltrating T cells in the synovial compartment. Etiologies based on triggering by bacteria are also considered: homologies between the ‘shared epitope’ sequences of HLA‐DR 1 and DR4 β chains, Escherichia coli dnaJ and Proteus haemolysin do not indicate any feasible mechanisms for the development of RA, and cannot explain the many cases in which such DR sequences do not occur, though new data from man and animals enhance interest in the role of bowel flora. Finally, the striking parallels between slow bacterial infections and RA, in terms of immunogenetics, pathology, IgG glycosylation abnormalities and autoimmune manifestations, are put forward as circumstantial evidence that such bacterial infections may underly, or trigger, this serious disease.