Experimental Autoimmune Encephalomyelitis of Mice: Catalytic Cross Site-Specific Hydrolysis of H1 Histone by IgG Antibodies Against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein

Introduction: Histones play crucial roles in chromatin functioning and gene transcription, but they are incredibly harmful in intercellular space since they stimulate systemic inflammatory and toxic responses.Myelin basic protein (MBP) is the most meaningful protein of the axon myelin-proteolipid sheath.Antibodies with different enzymatic activities (abzymes) are substantial and specific features of some autoimmune diseases. Methods: IgG preparations against individual histones (H1, H2A, H2B, H3, and H4) and MBP were obtained from the blood plasma of experimental autoimmune encephalomyelitis-prone C57BL/6 mice by several affinity chromatographies. These antibodies corresponded to different stages of experimental autoimmune encephalomyelitis (EAE) development: spontaneous, MOG (myelin oligodendrocyte glycoprotein), and DNA-histones complex accelerated onset, acute, and remission stages. Results: IgG-abzymes against MBP and five individual histones demonstrated unusual complex formation polyreactivity and enzymatic cross-reactivity in the specific hydrolysis of histone H1. All IgGs of 3-month-old mice (zero time) against MBP and individual histones demonstrated from 4 to 23 different H1 hydrolysis sites. The spontaneous achievement of EAE during 60 days led to a powerful change in the type and number of H1 hydrolysis sites by IgGs against five histones and MBP. Treatment of mice with MOG and DNA-histones complex results in alteration in IgGs activities, a change in type, and an increase or decrease in the number of H1 hydrolysis sites compared to zero time. The minimum number (4) of different H1 hydrolysis sites was found for IgGs against Н2B (zero time) and Н2A (MOG treatment), while the maximum (26) – against H1 (MOG treatment). Conclusion: Generally, it first demonstrated that at different stages of EAE evolution, IgG-abzymes against individual histones and MBP could significantly differ in specific sites and their number of H1 hydrolysis. Possible reasons for the catalytic cross-reactivity and strong differences in the number and type of cleavage sites are discussed.