Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia.
Department of Biomedicine, Siberian State Medical University, 634055 Tomsk, Russia.
Int J Mol Sci. 2022 Jul 2;23(13):7397. doi: 10.3390/ijms23137397.
The pathogenesis of bipolar affective disorder is associated with immunological imbalances, a general pro-inflammatory status, neuroinflammation, and impaired white matter integrity. Myelin basic protein (MBP) is one of the major proteins in the myelin sheath of brain oligodendrocytes. For the first time, we have shown that IgGs isolated from sera of bipolar patients can effectively hydrolyze human myelin basic protein (MBP), unlike other test proteins. Several stringent criteria were applied to assign the studied activity to serum IgG. The level of MBP-hydrolyzing activity of IgG from patients with bipolar disorder was statistically significantly 1.6-folds higher than that of healthy individuals. This article presents a detailed characterization of the catalytic properties of MBP-hydrolyzing antibodies in bipolar disorder, including the substrate specificity, inhibitory analysis, pH dependence of hydrolysis, and kinetic parameters of IgG-dependent MBP hydrolysis, providing the heterogeneity of polyclonal MBP-hydrolyzing IgGs and their difference from canonical proteases. The ability of serum IgG to hydrolyze MBP in bipolar disorder may become an additional link between the processes of myelin damage and inflammation.
双相情感障碍的发病机制与免疫失衡、普遍的促炎状态、神经炎症和白质完整性受损有关。髓鞘碱性蛋白（MBP）是脑少突胶质细胞髓鞘的主要蛋白之一。我们首次表明，从双相情感障碍患者血清中分离出的 IgG 可以有效地水解人髓鞘碱性蛋白（MBP），而不像其他测试蛋白那样。应用了几项严格的标准将所研究的活性分配给血清 IgG。与健康个体相比，双相情感障碍患者 IgG 的 MBP 水解活性统计学上高出 1.6 倍。本文详细描述了双相情感障碍中 MBP 水解抗体的催化特性，包括底物特异性、抑制分析、水解的 pH 依赖性和 IgG 依赖性 MBP 水解的动力学参数，提供了多克隆 MBP 水解 IgGs 的异质性及其与典型蛋白酶的区别。在双相情感障碍中，血清 IgG 水解 MBP 的能力可能成为髓鞘损伤和炎症过程之间的另一个联系。
