Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis
Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis
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DOI：
10.1371/journal.pone.0154688
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发表时间：
2016-05-19
期刊：
影响因子：
3.7
通讯作者：
Nevinsky, Georgy A.
中科院分区：
文献类型：
--
作者：
Doronin, Vasilii B.;Parkhomenko, Taisiya A.;Nevinsky, Georgy A.
我们最近发现MS患者血清和脑脊液(CSF)中的免疫球蛋白具有活跃的DNA和髓鞘碱性蛋白的水解性。根据文献资料，抗DNA和抗MBP抗体可能在这种慢性炎症性疾病和MS发病机制中促进重要的神经病理机制。同时，具有淀粉酶活性的抗体在任何自身免疫性疾病的发病机制中的作用尚未确定。脑脊液蛋白经G-琼脂糖凝胶顺序亲和层析和FPLC凝胶过滤，获得了电泳学和免疫学上均一的免疫球蛋白。我们首次提出了不可预测的证据，表明来自脑脊液的IGGS具有淀粉酶活性并能有效地降解麦芽七糖；它们的平均比抗体活性类似于来自相同MS患者血清的抗体的30倍。健康志愿者免疫球蛋白的特异性平均RA(SAA)约比MS患者低1000。此外，脑脊液总蛋白(包括抗体)的相对SAA比纯化的免疫球蛋白低15倍，而血清总蛋白的相对SAA比血清免疫球蛋白高1033倍。这一结果支持了脑脊液蛋白的淀粉酶活性主要是由淀粉酶活性引起的事实。不能排除脑脊液淀粉酶抗体在MS发病机制中的作用，并对其可能的原因进行了讨论。
We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is similar to 30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately similar to 1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) similar to 15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.