Synovial hyaluronate in rheumatoid arthritis

Acute inflammation of joints can lead to the development of chronic arthritis. The nature of agents that sustain the chronic inflammation remains an enigma, although infectious agents such as Rubella virus, Epstein-Barr virus or Chlamydia have been invoked. In most cases in which an inducing agent was sought, none was found.' However, several antigens have been identified that elicit acute arthritis in animal models. These include a 65 kDa Mycobacterium tuberculosis protein and isolated cell walls from streptococci. Increased titres against these antigens are also found in patients with rheumatoid arthritis. In addition, their sera cross react with cartilage specific collagen type II, link protein, proteoglycans, and heat shock proteins.' It is clear that these antigens are involved in acute arthritis in animal models, but it is not understood how they maintain the inflammatory response. Continuous production of chemotactic factors is necessary to attract granulocytes into the inflamed area. These chemotactic factors might be complement components that are produced during inflammation. The complement cascade can be initiated by the binding of Cl q to multimeric antigen-IgG complexes; such structures can be produced continuously in the synovial membrane. It is known that immune complexes in synovial fluid bind C 1 q and activate complement,3 resulting in decreased complement activity4 5 and an increased level of terminal complement complexes.6 However, no antigenic components are detectable in association with these immune complexes.7 12 The possibility was addressed that the critical antigens in chronic arthritis are generated continuously during the course of the inflammatory reaction. It is probable that a component specifically enriched in the joints, such as hyaluronate, is the key culprit, because hyaluronate is extensively degraded in the synovial membrane by the inflammatory reaction.13 The synovial fluids of patients with rheumatoid arthritis were therefore analysed for C 1 q binding immune complexes.