The investigation of autoantibody formation against oxidatively modified carbonic anhydrase and the relationship between these antibodies and some rheumatoid diseases

Carbonic anhydrase (CA) is a metalloenzyme with wide tissue distribution and in some rheumatoid disease autoantibodies formed against these enzymes. Recent studies have suggested that oxidative stres triggers anti-CA antibody formation. In this study we aimed to investigate the effects of CA modifications with 4-hydroxynonenal (HNE), malondialdehyde (MDA), peroxynitrite (PN) on CA autoantibody formation and the relationship between these antibodies and oxidant–antioxidant status in patients with rheumatoid arthritis (RA), ankylosing spondilitis (AS), Sjögren' s syndrome (SjS). In the present study CA I and CA II isoenzymes, isolated from erythrocytes, were modified with HNE, MDA and PN and the modification were verified with Western Blot analysis. Balb-c mice were immunized with these agents to determine the effects of the modification on antigenicity and also antibody titers were detected in the sera of mice. Autoantibody titers detected in individuals sera. In addition MDA, 4-HNE, 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured in serum and erythrocyte samples of the patients, thereby oxidant-antioxidant status was evaluated. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are cytokines which trigger antibody formation and inflamation, were measured and relationship between autoantibody and these molecules were determined. Patients PN-modified CA I and CA II autoantibody levels were found significantly different (p<0.05) in all groups compared with their controls. Significant difference was found between the autoantibody titers of both native and modified forms of CA and control groups (p<0.001). When modified forms compared with native forms in mice, it was found that HNE and MDA decreased the antigenicity while PN increased. In conclusion, oxidative modifications altered the antigenic properties of CA isoenzymes, especially PN modifications increased the antigenicity.