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


ŞENTÜRK A., ALVER A., KARKUCAK M., KÜÇÜK M., Rendi T. A.

AMERICAN JOURNAL OF THE MEDICAL SCIENCES, vol.366, no.6, pp.438-448, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 366 Issue: 6
  • Publication Date: 2023
  • Doi Number: 10.1016/j.amjms.2023.09.002
  • Journal Name: AMERICAN JOURNAL OF THE MEDICAL SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database
  • Page Numbers: pp.438-448
  • Karadeniz Technical University Affiliated: Yes

Abstract

Background: Carbonic 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 Sjoeurogren's syndrome (SjS).Methods: CA 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.Results: Modifications 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).Conclusions: PN 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.