Hydrolysis by catalytic IgGs of microRNA specific for patients with schizophrenia

Abstract

Significant importance of autoimmune changes in the pathogenesis of schizophrenia (SCZ) is not established. Here, we present the first evidence that autoantibodies of 100% SCZ patients possess RNase activity: сCMP > poly(C) > poly(A) > yeast RNA. In addition, we have got an unexpected result: there was revealed site-specific hydrolysis of four known SCZ specific microRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219a-5p) playing an important role in the regulation of several genes functioning. Three major of cleavage sites are located in the microRNA loops or duplex parts directly articulated with the loops. RNase abzymes can contribute to decreasing of microRNAs effects on the functioning of numerous genes and the products of their transcription. Therefore, abzymes with RNase activity may be to some extent important for the development of schizophrenia. © 2018 IUBMB Life, 70(2):153-164, 2018.

Natural Catalytic IgGs Hydrolyzing Histones in Schizophrenia: Are They the Link between Humoral Immunity and Inflammation?

“…In this work, we discovered antibodies hydrolyzing histones from the serum of patients with schizophrenia and described their biochemical properties. Earlier, we developed a method protocol for the isolation of electrophoretically homogeneous antibodies from different biological fluids that do not contain impurities of any canonical enzymes, which was used in numerous studies [ 17 , 30 , 31 , 32 , 33 , 34 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 47 , 48 , 50 ]. Fourteen previously proposed strict criteria were used to show that antibodies obtained using this method [ 26 , 30 , 31 , 32 , 33 , 34 ] do not contain impurities of any classical enzymes [ 30 , 31 , 32 , 33 , 34 ].…”

“…According to the results of a retrospective analysis for the same samples of schizophrenia IgGs, a clear positive correlation was found between the levels of hydrolysis of H1 and H4 with that for RNase activity (hydrolysis of miR-219-2-3p and miR-219-5p) [ 37 , 38 ], as well as activity in the hydrolysis of H1, H2a, and H4 with DNA-splitting activity [ 17 ] ( Table 4 ). Anti-DNA antibodies are known to generate against complexes of nucleic acids with various proteins, particularly to complexes of DNA with histones [ 24 , 25 ].…”

“…IgG preparations were obtained using affinity chromatography on the ÄKTA Start chromatograph (GE Healthcare) similar to previously published works [ 17 , 37 , 38 , 48 , 50 ]. The blood serum of patients and healthy donors (2 mL) was diluted four times with buffer A, consisting of 50 mM Tris-HCl, pH 7.5, and 150 mM NaCl.…”

“…It was shown that catalytic antibodies’ generation is the earliest and most substantial sign of impaired humoral immunity. Recently, we found catalytic antibodies with DNase and RNase activities, recognizing DNA and RNA and hydrolyzing non-specific homo-oligonucleotides, and site-specific microRNAs in patients with schizophrenia [ 17 , 37 , 38 ]. These observations are consistent with previously published data and indicate the formation of antinuclear antibodies directed against nucleic acids and nuclear proteins, including histones in schizophrenia [ 19 ].…”

<p>IgGs-Abzymes from the Sera of Patients with Systemic Lupus Erythematosus Hydrolyzed miRNAs</p>

“…26 Pathological processes resulting in inflammatory processes in SLE patients are associated with the change in miRNAs expression. 27 Taking into account a special role of miRNAs, it was interesting whether auto-Abs-abzymes against these miRNAs may be generated.…”