Molecules (Jan 2023)

Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice

  • Andrey E. Urusov,
  • Anna S. Tolmacheva,
  • Kseniya S. Aulova,
  • Georgy A. Nevinsky

DOI
https://doi.org/10.3390/molecules28031330
Journal volume & issue
Vol. 28, no. 3
p. 1330

Abstract

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The exact mechanisms of the evolution of multiple sclerosis are still unknown. At the same time, the development in C57BL/6 mice of experimental autoimmune encephalomyelitis (EAE, simulating human multiple sclerosis) happens as a result of the violation of bone marrow hematopoietic stem cell differentiation profiles integrated with the production of toxic auto-antibodies splitting the basic myelin protein, myelin oligodendrocyte glycoprotein (MOG), histones, and DNA. It has been shown that IgGs from the plasma of healthy humans and autoimmune patients oxidize many different compounds due to their peroxidase (H2O2-dependent) and oxidoreductase (H2O2-independent) activities. Here, we first analyzed the changes in the relative catalase activity of IgGs from C57BL/6 mice blood plasma over time at different stages of the EAE development (onset, acute, and remission phases). It was shown that the catalase activity of IgGs of 3-month-old mice is, on average, relatively low (kcat = 40.7 min−1), but it increases during 60 days of spontaneous development of EAE 57.4-fold (kcat = 2.3 × 103 min−1). The catalase activity of antibodies increases by a factor of 57.4 by 20 days after the immunization of mice with MOG (kcat = 2.3 × 103 min−1), corresponding to the acute phase of EAE development, and 52.7–fold by 60 days after the treatment of mice with a DNA–histone complex (kcat = 2.1 × 103 min−1). It is the acceleration of the EAE development after the treatment of mice with MOG that leads to the increased production of lymphocytes synthesizing antibodies with catalase activity. All data show that the IgGs’ catalase activity can play an essential role in reducing the H2O2 concentration and protecting mice from oxidative stress.

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