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IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs
Evgeny A Ermakov1, Evelina M Kabirova1, Valentina N Buneva1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave, 630090 Novosibirsk, Russia.
Abstract:
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.
Insights
Multiple sclerosis (MS) patients
Area of Science:
- Immunology
- Neuroscience
- Molecular Biology
Background:
- Autoantibodies, previously identified as abzymes, can hydrolyze DNA, myelin basic protein, and oligosaccharides.
- Specific microRNAs (miRNAs) show increased expression in the blood and cerebrospinal fluid of multiple sclerosis (MS) patients.
- Autoantibodies capable of hydrolyzing miRNAs were initially discovered in schizophrenia patients.
Purpose of the Study:
- To investigate the recognition and hydrolytic activity of IgG autoantibodies from MS patients against neuroregulatory and immunoregulatory miRNAs.
- To characterize the specificity and efficiency of miRNA hydrolysis by MS patient-derived IgGs.
Main Methods:
- Detection and characterization of IgG autoantibodies in the sera of MS patients.
- Assay of IgG autoantibody recognition and hydrolysis of eight specific miRNAs (four neuroregulatory, four immunoregulatory).
- Analysis of hydrolysis site specificity and relative activity (RA) of IgGs against miRNAs.
- Statistical comparison of RA between MS patient groups and healthy donors.
Main Results:
- MS patient IgG antibodies were found to effectively recognize and hydrolyze eight specific neuroregulatory and immunoregulatory miRNAs.
- Hydrolysis was predominantly site-specific, with consistent major and moderate cleavage sites across most IgG preparations.
- Significant differences in miRNA hydrolysis relative activity were observed between MS patients and healthy donors (p < 0.015).
- A trend towards decreased miRNA hydrolysis efficiency was noted during disease remission compared to exacerbation.
Conclusions:
- IgG autoantibodies in MS patients possess the intrinsic ability to recognize and hydrolyze specific neuroregulatory and immunoregulatory miRNAs.
- The hydrolysis activity is largely site-specific, though variations exist among individuals and specific IgG preparations.
- The findings suggest a potential role for these miRNA-hydrolyzing autoantibodies in the pathogenesis or as biomarkers of multiple sclerosis, with activity varying with disease state.
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