ANTIBODIES TO CYTOKERATINS IN INFLAMMATORY ARTHROPATHIES

Objectives: Cytokeratins are a major constituent of the cytoskeleton i n eukaryotic cells and are vital for the maintenance of cell structure and function, Identification of increased levels of IgA antibodies to these intracellular structures has prompted increasing interest in th e potential role between the gut and the immune system in the pathogen esis of inflammatory arthritis. This review examines the salient featu res of cytokeratin (CK) antibodies that are relevant to inflammatory a rthropathies and discusses the meaning and potential applications of t hese findings in the context of the different arthropathies. Methods: Review of the literature on antibodies to cytokeratins in inflammtory arthropathies, using MEDLINE and the key words (cyto)keratin and arthr itis. The studies were interpreted and critiqued. Results: Increased l evels of IgA antibodies to CK-18 and epidermal keratins have been show n by enzyme-linked immunosorbent assay (ELISA) in rheumatoid arthritis and psoriatic arthritis. Levels were not increased in osteoarthritis or reactive arthritis. Conclusions: CK-18 is present within endothelia l cells lining synovial blood vessels in patients with various rheumat ic conditions, including rheumatoid arthritis, as well as in normal co ntrols. Damage to synovial endothelial cells may lead to increased pro duction of antibodies to CK-18. The CK antibody response is independen t of the polyclonal immunoglobulin expansion typical of RA and is not specific for RA because an increased IgA response to CK-18 also has be en shown in psoriasis and in psoriatic arthritis. Damage to synovial e ndothelial cells does not explain the increased autoantibody productio n in other conditions such as psoriasis. In this condition, damage to epithelial tissues in other regions of the body (eg, skin, gut, kidney ) may lead to production of keratin antibodies that recognize epitopes common to all CK, including CK-18. The reason for an elevated IgA ant i-CK response rather than an IgG or IgM response is not clear. It cann ot be explained by a general increase in serum IgA levels. Most of the conditions in which raised levels of these antibodies were found have been associated to different degrees with abnormalities of the gut mu cosa or mucosal immune system. It appears that the nature of autoantib odies to CK-18 is probably natural rather than pathogenic, Currently t here are no data on the source of the IgA antibodies to cytokeratins ( ie, mucosal or central immune system). Indeed, it may depend on the di sease. Copyright (C) 1997 by W.B. Saunders Company.