Antibodies to cytokeratins in inflammatory arthropathies

Objectives: Cytokeratins are a major constituent of the cytoskeleton in 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 the potential role between the gut and the immune system in the pathogenesis of inflammatory arthritis. This review examines the salient features of cytokeratin (CK) antibodies that are relevant to inflammatory arthropathies and discusses the meaning and potential applications of these 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 arthritis. The studies were interpreted and critiqued. Results: Increased levels of IgA antibodies to CK-18 and epidermal keratins have been shown 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 endothelial cells lining synovial blood vessels in patients with various rheumatic conditions, including rheumatoid arthritis, as well as in normal controls. Damage to synovial endothelial cells may lead to increased production of antibodies to CK-18. The CK antibody response is independent of the polyclonal immunoglobulin expansion typical of RA and is not specific for RA because an increased IgA response to CK-18 also has been shown in psoriasis and in psoriatic arthritis. Damage to synovial endothelial cells does not explain the increased autoantibody production 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 anti-CK response rather than an IgG or IgM response is not clear. It cannot 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 mucosa or mucosal immune system. It appears that the nature of autoantibodies to CK-18 is probably natural rather than pathogenic, Currently there are no data on the source of the IgA antibodies to cytokeratins (ie, mucosal or central immune system). Indeed, it may depend on the disease. Copyright (C) 1997 by W.B. Saunders Company.