Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Molecules. 2022 Nov 3;27(21):7527. doi: 10.3390/molecules27217527.
The exact mechanisms of multiple sclerosis development are still unknown. However, the development of EAE (experimental autoimmune encephalomyelitis) in Th and 2D2 mice is associated with the infringement of the differentiation profiles of bone marrow hematopoietic stem cells which are bound with the production of compounds that are harmful for human autoantibodies-abzymes that hydrolyze myelin oligodendrocyte glycoprotein, myelin basic protein, and DNA. It showed that autoimmune patients' antioxidant IgG antibodies oxidise some compounds due to their peroxidase (HO-dependent) and oxidoreductase (HO-independent) activities more effectively than those in healthy humans can. It was interesting to identify whether the redox activities of the antibodies change during the development of autoimmune diseases. Here, we analyzed the change in these redox activities of the IgGs from the blood of Th and 2D2 mice, which corresponded to different stages of the EAE development. The peroxidase activity in the oxidation of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) in the Th (4-fold) and 2D2 (2-fold) mice IgGs, on average, is higher than the oxidoreductase activity is. The peroxidase activity of the Th (1.9-fold) and 2D2 (3.5-fold) mice IgGs remarkably increased during the 40 days of the spontaneous development of EAE. Forty days after the immunization of the MOG peroxidase activity, the IgGs of the Th and 2D2 mice increased 5.6-6.0 times when they were compared with those that presented no increase (3 months of age). The mice IgGs were oxidized with 3,3'-diaminobenzidine (2.4-4.3-fold) and o-phenylenediamine (139-143-fold) less efficiently than they were with ABTS. However, the temper of the change in the IgG activity in the oxidation of these substrates during the spontaneous and MOG-induced development of EAE was close to that which occurred for ABTS. All of the data show that the IgG peroxidase and oxidoreductase activities of EAE mice can play an important role in their protection from toxic compounds and oxidative stress.
多发性硬化症的确切发病机制尚不清楚。然而,实验性自身免疫性脑脊髓炎(EAE)在 Th 和 2D2 小鼠中的发展与骨髓造血干细胞分化谱的侵犯有关,这些分化谱与产生对人类自身抗体有害的化合物有关,即水解髓鞘少突胶质细胞糖蛋白、髓鞘碱性蛋白和 DNA 的 abzymes。研究表明,与健康人相比,自身免疫性疾病患者的抗氧化 IgG 抗体由于其过氧化物酶(HO 依赖性)和氧化还原酶(HO 非依赖性)活性,更有效地氧化一些化合物。有趣的是,确定自身抗体的氧化还原活性是否在自身免疫性疾病的发展过程中发生变化。在这里,我们分析了来自处于 EAE 发展不同阶段的 Th 和 2D2 小鼠血液中的 IgG 的这些氧化还原活性变化。Th(4 倍)和 2D2(2 倍)小鼠 IgG 中 ABTS(2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid))氧化的过氧化物酶活性平均高于氧化还原酶活性。在 EAE 自发发展的 40 天内,Th(1.9 倍)和 2D2(3.5 倍)小鼠 IgG 的过氧化物酶活性显著增加。在 MOG 过氧化物酶免疫接种后 40 天,与未增加的 IgG 相比,Th 和 2D2 小鼠的 IgG 增加了 5.6-6.0 倍(3 个月大)。与 ABTS 相比,3,3'-二氨基联苯胺(2.4-4.3 倍)和邻苯二胺(139-143 倍)氧化小鼠 IgG 的效率较低。然而,在自发和 MOG 诱导的 EAE 发展过程中,这些底物的 IgG 活性变化的温度与 ABTS 相似。所有数据表明,EAE 小鼠的 IgG 过氧化物酶和氧化还原酶活性可以在保护它们免受有毒化合物和氧化应激方面发挥重要作用。