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

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.

IgGs-Abzymes from the Sera of Patients with Systemic Lupus Erythematosus Hydrolyzed miRNAs.

BACKGROUND AND OBJECTIVES: Systemic lupus erythematosus (SLE) is an inflammatory disease. The sera of SLE patients contain antibodies-abzymes hydrolyzing myelin basic protein (MBP), DNA, nucleotides, and oligosaccharides. The blood of SLE patients contains an increased amount of some specific miRNAs. This study aimed to analyze a possible hydrolysis of eight microRNAs found in the blood of SLE patients with high frequency by blood antibodies-abzymes. PATIENTS AND METHODS: Using affinity chromatography of the serum proteins of SLE patients and healthy donors on protein G-Sepharose and following FPLC gel filtration, electrophoretically homogeneous IgG preparations containing no impurities of canonical RNases were obtained. These preparations were used to analyze their activity in the hydrolysis of eight miRNAs. RESULTS: It was shown that SLE IgGs hydrolyze very efficiently four neuroregulatory miRNAs (miR-219-2-3p, miR-137, miR-219a-5p, and miR-9-5p) and four immunoregulatory miRNAs (miR-326, miR-21-3p, miR-155-5p, and miR-146a-3p). To demonstrate that the miRNAs hydrolysis is an intrinsic property of SLE IgGs, several rigid criteria were checked. Only some IgGs of healthy donors showed very weak, but reliably detectable activity in the hydrolysis miRNAs. The average activity of SLE patients IgGs according to median values is statistically significant 84.8-fold higher than that of healthy donors. The maximum and comparable average activity (RA) was observed in the hydrolysis of three miRAs: miR-9-5p, miR-155-5p, and miR-326. MiR-9-5p plays an important role in the development of lupus nephritis, while miR-326 activates the production of antibodies by B cells. The major and moderate specific sites of the hydrolysis of each miRNA were revealed. The hydrolysis of eight microRNAs was mostly site specific. Several SLE IgGs hydrolyzed some miRNAs demonstrating a combination of site-specific and non-specific splitting. CONCLUSION: Since inflammatory processes in SLE are associated with the change in miRNAs expression, the decrease in their concentration due to hydrolysis by autoantibodies-abzymes may be important for SLE pathogenesis.