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Autoantibodies-Abzymes with Phosphatase Activity in Experimental Autoimmune Encephalomyelitis Mice
Andrey E Urusov1,2, Kseniya S Aulova1, Georgy A Nevinsky1,2
1Institute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, 630090 Novosibirsk, Russia.
Abstract:
The exact mechanisms of MS (multiple sclerosis) evolution are still unknown. However, the development of EAE (experimental autoimmune encephalomyelitis simulating human MS) in C57BL/6 mice occurs due to the violation of bone marrow hematopoietic stem cell differentiation profiles, leading to the production of toxic for human autoantibody splitting MBP (myelin basic protein), MOG (mouse oligodendrocyte glycoprotein), five histones, DNA, and RNA. Here, we first analyzed the changes in the relative phosphatase activity of IgGs from C57BL/6 mice blood over time, corresponding to three stages of EAE: onset, acute, and remission. Antibodies have been shown to catalyze the hydrolysis of p-nitrophenyl phosphate at several optimal pH values, mainly in the range of 6.5-7.0 and 8.5-9.5. During the spontaneous development of EAE, the most optimal value is pH 6.5. At 50 days after the birth of mice, the phosphatase activity of IgGs at pH 8.8 is 1.6-fold higher than at pH 6.5. During spontaneous development of EAE from 50 to 100 days, an increase in phosphatase activity is observed at pH 6.5 but a decrease at pH 8.8. After mice were immunized with DNA-histone complex by 20 and 60 days, phosphatase activity increased respectively by 65.3 and 109.5 fold (pH 6.5) and 128.4 and 233.6 fold (pH 8.8). Treatment of mice with MOG at the acute phase of EAE development (20 days) leads to a maximal increase in the phosphatase activity of 117.6 fold (pH 6.5) and 494.7 fold (pH 8.8). The acceleration of EAE development after mice treatment with MOG and DNA-histone complex results in increased production of lymphocytes synthesizing antibodies with phosphatase activity. All data show that IgG phosphatase activity could be essential in EAE pathogenesis.
Insights
This study reveals that immunoglobulin G (IgG) phosphatase activity significantly increases during experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. This heightened activity, particularly at specific pH levels, is linked to disease progression and suggests a key role for IgG in EAE pathogenesis.
Area of Science:
- Immunology
- Biochemistry
- Neuroscience
Background:
- The precise mechanisms driving multiple sclerosis (MS) progression remain elusive.
- Experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice serves as a model for human MS.
- EAE development involves altered bone marrow hematopoietic stem cell differentiation, producing autoantibodies against myelin basic protein (MBP), mouse oligodendrocyte glycoprotein (MOG), histones, DNA, and RNA.
Purpose of the Study:
- To investigate the changes in relative phosphatase activity of immunoglobulin G (IgG) in C57BL/6 mice during different stages of EAE.
- To determine the optimal pH conditions for IgG phosphatase activity in the context of EAE.
- To explore the correlation between IgG phosphatase activity and EAE development following immunization and treatment.
Main Methods:
- Analysis of IgG phosphatase activity in mouse blood sera across EAE onset, acute, and remission phases.
- Assay of IgG's catalytic hydrolysis of *p*-nitrophenyl phosphate at various pH values.
- Monitoring of phosphatase activity changes after immunization with DNA-histone complex and treatment with MOG during EAE.
Main Results:
- IgG exhibited optimal phosphatase activity at pH 6.5-7.0 and 8.5-9.5.
- During spontaneous EAE, activity at pH 6.5 increased, while activity at pH 8.8 decreased between 50 and 100 days.
- Immunization and MOG treatment markedly elevated IgG phosphatase activity, correlating with accelerated EAE development and increased lymphocyte production of these antibodies.
Conclusions:
- IgG phosphatase activity demonstrates significant alterations during the spontaneous and induced development of EAE.
- The observed changes in IgG phosphatase activity, particularly its increase under specific conditions, suggest a critical role in the pathogenesis of EAE.
- Further research into IgG phosphatase activity could offer insights into MS mechanisms and potential therapeutic targets.
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