Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 630090 Lavrentiev, Russia.
Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, 690022 Vladivostok, Russia.
Biomolecules. 2020 Oct 30;10(11):1501. doi: 10.3390/biom10111501.
Anti-DNA antibodies are usually produced against histone-DNA complexes appearing during cell apoptosis, while histones are known as damage-associated molecules. A myelin sheath of axons contains myelin basic protein (MBP) playing an important role in the pathogenesis of autoimmune diseases. Antibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Abzymes against different proteins can usually only hydrolyze these specific proteins. Using sequential chromatographies of homogeneous IgG preparations from sera of HIV-infected patients on columns with immobilized MBP, H2a, and H2b histones, the anti-MBP, anti-H2a, and anti-H2b antibodies were obtained. It was first shown that IgGs against H2a and H2b effectively hydrolyze these histones and MBP, while anti-MBP split MBP, H2a, and H2b, but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H2a, H2b, and MBP by abzymes against these three proteins were found. Among 14 sites of hydrolysis of H2a by IgGs against H2a and 10 sites by anti-MBP IgGs, only one site of hydrolysis was the same for these abzymes. Eleven cleavage sites of H2b with IgGs against H2b and 10 sites of its hydrolysis with antibodies against MBP were different. Anti-H2a, anti-H2b, and anti-MBP abzymes are unpredictable examples of IgGs possessing not only cross-complexation but also catalytic cross-reactivity, which may be a common phenomenon for such abzymes in patients with different autoimmune diseases. The existence of cross-reactivity of abzymes against H2a and H2b histones and MBP represent a great danger to humans since, in contrast with MBP, histones due to cell apoptosis constantly occur in human blood. Anti-H2a, anti-H2b, and anti-MBP can attack and hydrolyze myelin basic protein of the myelin sheath of axons and plays a negative role in the pathogenesis of several pathologies.
抗 DNA 抗体通常针对细胞凋亡过程中出现的组蛋白-DNA 复合物产生，而组蛋白是众所周知的损伤相关分子。轴突的髓鞘含有髓鞘碱性蛋白 (MBP)，在自身免疫性疾病的发病机制中发挥重要作用。具有酶活性的抗体（abzymes）是某些自身免疫性和病毒性疾病的独特特征。针对不同蛋白质的 abzymes通常只能水解这些特定的蛋白质。使用从 HIV 感染患者血清中分离的均一组分 IgG 进行连续色谱分析，在固定化 MBP、H2a 和 H2b 组蛋白的柱上进行，获得了抗 MBP、抗 H2a 和抗 H2b 抗体。首次表明，针对 H2a 和 H2b 的 IgG 有效地水解这些组蛋白和 MBP，而抗 MBP 则分裂 MBP、H2a 和 H2b，但不分裂其他对照蛋白。使用 MALDI 质谱法，发现了针对这三种蛋白质的 abzymes 对 H2a、H2b 和 MBP 的切割位点。针对 H2a 的 IgG 水解 H2a 的 14 个位点和抗 MBP IgG 水解 H2a 的 10 个位点中，只有一个位点的水解是这些 abzymes相同的。针对 H2b 的 IgG 水解 H2b 的 11 个位点和针对 MBP 的抗体水解 H2b 的 10 个位点不同。抗 H2a、抗 H2b 和抗 MBP abzymes 是 IgG 具有不仅交叉络合而且催化交叉反应性的不可预测的例子，这可能是患有不同自身免疫性疾病的患者中此类 abzymes 的常见现象。针对 H2a 和 H2b 组蛋白和 MBP 的 abzyme 的交叉反应性的存在对人类构成了巨大的危险，因为与 MBP 不同，由于细胞凋亡，组蛋白在人类血液中不断出现。抗 H2a、抗 H2b 和抗 MBP 可以攻击和水解轴突髓鞘的髓鞘碱性蛋白，并在几种病理学的发病机制中发挥负面作用。
