Macka Vocational School, Karadeniz Technical University, Trabzon 61750, Türkiye.
Faculty of Medicine, Department of Medical Biochemistry, Karadeniz Technical University, Trabzon, Türkiye.
Am J Med Sci. 2023 Dec;366(6):438-448. doi: 10.1016/j.amjms.2023.09.002. Epub 2023 Sep 9.
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 Sjögren's syndrome (SjS).
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.
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).
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.
碳酸酐酶（CA）是一种金属酶，具有广泛的组织分布，参与许多重要的生理过程，在一些风湿性疾病中，针对这些酶会形成自身抗体。最近的研究表明，氧化应激会引发抗 CA 抗体的形成。在这项研究中，我们旨在研究氧化/硝化应激终产物对小鼠 CA 抗原性的影响，以及类风湿关节炎（RA）和干燥综合征（SjS）患者中修饰 CA 自身抗体与氧化还原状态之间的关系。
从人红细胞中分离出 CA I 和 CA II 同工酶，并分别用 4-羟基壬烯醛（4-HNE）、丙二醛（MDA）和过氧亚硝酸盐（PN）修饰。用这些试剂免疫 Balb-c 小鼠，以确定修饰对 CA 抗原性的影响。检测患者修饰 CA 同工酶的自身抗体滴度。此外，还测量了丙二醛（MDA）、4-羟基壬烯醛（4-HNE）、3-硝基酪氨酸（3-NT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性，以评估患者的氧化还原状态。
用氧化应激终产物 HNE、MDA 和 PN 修饰碳酸酐酶会导致小鼠对这些酶的免疫反应发生变化。结果发现 HNE 和 MDA 降低了抗原性，而 PN 则增加了抗原性。此外，还发现 RA 和 SjS 患者的 PN 修饰 CA 自身抗体水平与对照组相比有显著差异（p<0.05）。
PN 修饰也可以在小鼠中引发针对 CA 同工酶的免疫反应，并且在 RA 和 SjS 患者中发现 PN 修饰的 CA I 和 CA II 自身抗体滴度显著升高。
