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Premises for immune interventional therapy in rheumatoid arthritis.
  1. I. R. Mackay,
  2. M. J. Rowley
  1. Clinical Research Unit, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

    Abstract

    Consideration of rheumatoid arthritis (RA) as an autoimmune disease includes initiating event(s), genetic predisposition, immune regulatory derangements, and effector cycles of articular damage. The initiating event is still unknown. Collagen type 2 has good claims as a rheumatogenic autoantigen which perpetuates disease. The association of HLA DR4 with rheumatoid arthritis is in part explainable by the affinity of binding of the rheumatogenic antigen to a hypervariable portion of MHC Class II molecules with selective presentation of this complex to T cell receptors. Immune regulatory derangements include lymphokine-induced aberrant expression of MHC Class II molecules on synovial tissues, the presence of a 'resistant' subset of B cells (CD5 + ve), failure of anti-idiotypic control of autoantibodies (not well established as yet in rheumatoid arthritis), and defective immune suppression, revealed by low counts in synovial fluids of a suppressor-inducer subset of CD4 + ve T cells. The many possibilities for therapeutic immune intervention would include polyclonal or monoclonal antibody to block (a) receptors for antigen on B or T lymphocytes (but this would require knowledge of the rheumatoid arthritis-inducing antigen), (b) the CD4 complex on helper T lymphocytes, (c) MHC Class II (Ia) molecules, for which there are excellent prototypes in experimental immunopathology, or (d) lymphokines or their receptors. Induction of suppression by 'tolerogenic vaccines' is experimentally validated, but only for diseases for which an autoantigen can be identified.

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