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IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs

机译:来自多发性硬化症患者血清的IgGS-Abzymes认可和水解miRNA

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摘要

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Here, we present the first evidence that 23 IgG antibodies of MS patients effectively recognize and hydrolyze four neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219-5p) and four immunoregulatory miRNAs (miR-21-3p, miR-146a-3p, miR-155-5p, and miR-326). Several known criteria were checked to show that the recognition and hydrolysis of miRNAs is an intrinsic property of MS IgGs. The hydrolysis of all miRNAs is mostly site-specific. The major and moderate sites of the hydrolysis of each miRNA for most of the IgG preparations coincided; however, some of them showed other specific sites of splitting. Several individual IgGs hydrolyzed some miRNAs almost nonspecifically at nearly all internucleoside bonds or demonstrated a combination of site-specific and nonspecific splitting. Maximum average relative activity (RA) was observed in the hydrolysis of miR-155-5p for IgGs of patients of two types of MS—clinically isolated syndrome and relapsing-remitting MS—but was also high for patients with primary progressive and secondary progressive MS. Differences between RAs of IgGs of four groups of MS patients and healthy donors were statistically significant (p < 0.015). There was a tendency of decreasing efficiency of hydrolysis of all eight miRNAs during remission compared with the exacerbation of the disease.
机译:在多发性硬化症(MS)的患者的血清中,揭示了自身抗体 - 释放水解DNA,髓鞘碱性蛋白质和低聚糖。在MS中,在血液和脑脊液中发现特异性微小液,其表征增加。在精神分裂症患者的血液中首先检测到自身抗体,特别是水解四种不同的miRNA。在这里,我们提出了第一种证据,即MS患者的23个IgG抗体有效地识别和水解四个神经疗程miRNA(miR-137,miR-9-5p,miR-219-2-3p和miR-219-5p)和四种免疫调节剂miRNA(miR-21-3p,miR-146a-3p,miR-155-5p和miR-326)。检查了几种已知标准以表明MiRNA的识别和水解是MS IgGS的内在性质。所有miRNA的水解主要是特异性的。对于大多数IgG制剂,每个miRNA的水解的主要和中等位点吻合;然而,其中一些人展示了其他特定的分裂部位。几个单独的IgG在几乎所有的核苷键处几乎不渗透地水解了一些miRNA,或者表现出特异性和非特异性分裂的组合。在MIR-155-5P的水解中观察到最大平均相对活性(RA)用于两种类型的MS型临床综合征患者的IGG和复发 - 延长MS-OR的患者,但对初级渐进和次级逐步的患者也很高。四组MS患者和健康供体的IgGS的RA之间的差异有统计学意义(P <0.015)。与疾病的加剧相比,缓解后,在缓解期间,患有八种miRNA的水解效率的趋势。

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