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

Abstract

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 autoantibodiesabzymes may be important for SLE pathogenesis.

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

“…Interestingly, the average efficiencies of hydrolysis of four of these miRNAs, with 21 Abs preparations from sera of patients with schizophrenia (average value 61.6 ± 32.7, M = 62.9, IQR = 60.6%) [ 43 , 44 ] and 23 patients with MS (average value 51.2 ± 35.8, M =45.8, IQR =71.3%), were only slightly different. A similar situation for these four miRNAs was observed for 11 IgG preparations of SLE patients (average value 56.0 ± 29.8, M = 56.7, IQR = 30.1%) [ 66 ]. At the same time, there are some differences in relative activities in the hydrolysis of some -RNAs by IgGs of patients with MS, SLE, and schizophrenia.…”

“…It has been shown recently that antibodies from the blood of schizophrenia [ 43 , 44 ] and SLE [ 66 ] patients effectively hydrolyze four individual miRNAs: miR-137, miR-9-5p, miR-219-2-3p, and miR-219a-5p. The blood of patients with MS and SLE contains abzymes that recognize and hydrolyze several of their own antigens: MBP, DNA, histones, and oligosaccharides [ 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

“…At the same time, there are some differences in relative activities in the hydrolysis of some -RNAs by IgGs of patients with MS, SLE, and schizophrenia. The maximum and minimum activity of IgGs in MS patients is observed in the case of miR-155-5p and miR-137, respectively, while it is observed for SLE antibodies for miR-9-5p and miR-219a-5p [ 66 ] and for abzymes of schizophrenia patients for miR-219a-5p and miR-219a-2-3p [ 43 , 44 ].…”

“…Overall, the sera of schizophrenia, MS, and SLE patients contain several common neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, miR-219-5p), whereas in immunoregulation, the sera contain miR-21-3p, miR-146a-3p, miR-155-5p, miR-326, and some other microRNAs [ 37 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. In addition, it was shown recently that IgGs from the blood of SLE patients also efficiently hydrolyzed these eight microRNAs [ 66 ]. Such similarity in the increase in the expression of these regulatory miRNAs in patients with MS, SLE, and schizophrenia may lead to the appearance of some common features in these diseases.…”

Antibodies as Biosensors’ Key Components: State-of-the-Art in Russia 2020–2021

“…This reflects the peculiarity of the immunological reactivity of the organism during this disease. Autoantibodies-abzymes-that hydrolyze microRNAs were found in the sera of patients with multiple sclerosis and systemic lupus erythematosus [111,112]. Evidence has been presented that the secretory IgA molecules of breast milk (but not the blood sera of healthy men and non-pregnant women) can effectively hydrolyze ribooligonucleotides, i.e., they are abzymes that effectively hydrolyze microRNAs in their loop and duplex regions.…”