Rheumatoid arthritis and gut related lymphocytes: the iteropathy concept.

The aetiology of rheumatoid arthritis (RA) remains unknown. The involvement of the gut in reactive arthritis (ReA) and of the genitourinary system in Reiter's syndrome (RS), though recognised, is poorly understood. Distribution of phlogistic products via Batson's plexus has been suggested to account for the distribution of involved joints in these conditions.' Ankylosing spondylitis (AS) too has been associated with gut bacteria, including Klebsiella pneumoniae.2 It is possible that sulphasalazine, for which efficacy has been claimed in all these conditions,46 may mediate its effects by immunosuppression of the gut associated lymphoid tissue (GALT). This is because only at concentrations above those found in the blood stream is it immunosuppressive in vitro.7 If this also applies in vivo it opens up a whole new vista of possibilities regarding the aetiopathogenesis of these disorders. The gut is a lymphoid organ at the heart of the secretory immune system, which is known to be involved in immune protection at mucosal surfaces and is largely mediated by IgA. It also includes certain other sites, however, which, though not strictly mucosal, have functions that are anatomically and functionally close. These include the salivary, lacrimal, and mammary glands. There is a reasonable body of evidence to indicate that these sites are normally colonised by lymphocytes or plasma cells, or both, that have seeded there from GALT,-'-3 which is regarded as the major component of the mucosa associated lymphoid tissue. Mucosa associated lymphoid tissue comprises certain other sites, including the bronchi associated lymphoid tissue and the genitourinary tract lymphoid tissue. Homing tendencies of lymphocytes appear to be determined by adhesins, 14 detectable using monoclonal anti-