• Am. J. Med. Sci. · Dec 2023

    Oxidative modification of carbonic anhydrase by peroxynitrite trigger immune response in mice and rheumatic disease patients.

    • Ayse Senturk, Ahmet Alver, Murat Karkucak, Murat Küçük, and Ahmadi RendiTaghiTGraduate School of Medical Science, Department of Medical Biochemistry, Karadeniz Technical University, Trabzon, Türkiye; Faculty of Medicine, Department of Medical Biochemistry, Istanbul University, Istanbul, Turkey..
    • Macka Vocational School, Karadeniz Technical University, Trabzon 61750, Türkiye. Electronic address: aysesenturk@ktu.edu.tr.
    • Am. J. Med. Sci. 2023 Dec 1; 366 (6): 438448438-448.

    BackgroundCarbonic anhydrases (CA) are metalloenzymes with wide tissue distribution, involved in many important physiological processes, and in some rheumatic diseases, autoantibodies are formed against these enzymes. Recent studies have suggested that oxidative stress triggers anti-CA antibody formation. In this study, we aimed to investigate the effects of modification with oxidative/nitrosative stress end products on CA antigenicity in mice and the relationship between the modified CA autoantibodies and oxidant-antioxidant status in patients with rheumatoid arthritis (RA) and Sjögren's syndrome (SjS).MethodsCA I and CA II isoenzymes were isolated from human erythrocytes and modified with 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and peroxynitrite (PN). Balb-c mice were immunized with these agents to determine the effects of modification on CA antigenicity. The autoantibody titers of modified CA isoenzymes were detected in patients. In addition MDA, 4-HNE, 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured to assess the oxidant-antioxidant status in patients.ResultsModifications of carbonic anhydrase with oxidative stress end products, HNE, MDA and PN, lead to alterations in the immune response to these enzymes in mice. It was found that HNE and MDA decreased the antigenicity while PN increased. In addition, PN-modified CA autoantibody levels were found to be significantly different in both RA and SjS patients compared to their controls (p<0.05).ConclusionsPN modifications can also trigger an immune response against CA isoenzymes in mice, and PN-modified CA I and CA II autoantibody titers were found at a significantly high level in both RA and SjS patients.Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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