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Autoantibody-Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
Andrey E Urusov1, Anna S Tolmacheva1, Kseniya S Aulova1
1Institute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, Novosibirsk 630090, Russia.
Abstract:
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.
Insights
Immunoglobulin G (IgG) from mice with experimental autoimmune encephalomyelitis (EAE) exhibits significantly increased catalase activity. This heightened activity may protect against oxidative stress during EAE development, a model for multiple sclerosis.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- The precise mechanisms driving multiple sclerosis (MS) remain elusive.
- Experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice mimics MS and involves aberrant hematopoietic stem cell differentiation and auto-antibody production targeting myelin oligodendrocyte glycoprotein (MOG), histones, and DNA.
- Immunoglobulin G (IgG) possesses peroxidase and oxidoreductase activities, influencing compound oxidation.
Purpose of the Study:
- To investigate the changes in relative catalase activity of IgGs during various stages of EAE development in C57BL/6 mice.
- To explore the potential role of IgG catalase activity in mitigating oxidative stress during EAE.
Main Methods:
- Analysis of relative catalase activity (kcat) of IgGs isolated from C57BL/6 mice blood plasma.
- Measurement of IgG catalase activity at different time points during spontaneous EAE development (onset, acute, remission phases).
- Assessment of IgG catalase activity following immunization with MOG or treatment with a DNA-histone complex.
Main Results:
- Baseline IgG catalase activity in 3-month-old mice was low (kcat = 40.7 min⁻¹).
- Catalase activity of IgGs increased significantly (57.4-fold) during 60 days of spontaneous EAE development (kcat = 2.3 × 10³ min⁻¹).
- A 57.4-fold increase in IgG catalase activity was observed by day 20 post-MOG immunization (acute EAE phase), and a 52.7-fold increase by day 60 post-DNA-histone complex treatment (kcat = 2.1 × 10³ min⁻¹).
Conclusions:
- IgG catalase activity substantially increases during EAE development in mice.
- Accelerated EAE progression, particularly after MOG immunization, correlates with increased production of lymphocytes synthesizing catalase-active antibodies.
- Elevated IgG catalase activity likely plays a crucial role in reducing hydrogen peroxide (H₂O₂) levels, thereby protecting against oxidative stress in EAE.
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