Introduction: Histones play vital roles in gene transcription and chromatin functioning, but they are very harmful since, in intercellular space, they stimulate toxic responses and systemic inflammation. Myelin basic protein (MBP) is the most important protein of the axon myelin-proteolipid sheath. Antibodies with various catalytic activities (abzymes; Abzs) are very specific features of some autoimmune diseases. 
Methods: IgGs against individual histones (H3, H1, H2A, H2B, and H4) and MBP were isolated from the blood plasma of experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice by several affinity chromatographies. These IgGs corresponded to different stages of EAE evolution: spontaneous, myelin oligodendrocyte glycoprotein (MOG), and complex of DNA with histones accelerated onset, acute, and remission stages. 
Results: IgG-Abzs against MBP and five individual histones showed unusual complexation polyreactivity and enzymatic cross-reactivity in the specific hydrolysis of H3 histone. All IgGs at zero time (3-month-old mice) against MBP and five individual histones according to MALDI mass spectrometry demonstrated from 5 to 21 different H3 hydrolysis sites. The spontaneous evolution of EAE during 60 days results depending on IgGs against various histones in a powerful increase or decrease in the type and number of H3 hydrolysis sites. Mice treatment with MOG or DNA-histones complex leads to changes in IgGs activities and a specific alteration in type and number of H3 hydrolysis sites in comparison with sites corresponding to zero time and spontaneous development of EAE. The minimum number (5) of different H3 hydrolysis sites was revealed for IgGs against ?4 (60 days after immunization of mice with DNA-histones complex), while the maximum (21) to IgGs against H1 and MBP (60 days after spontaneous EAE development). 
Conclusion: It first was shown that at various stages of EAE development and mice immunization with different antigens, IgG-abzymes against five individual histones and MBP could significantly differ in relative specific activities and number and type of particular sites of H3 hydrolysis. Possible reasons for such catalytic cross-reactivity and strong differences in the type and number of the splitting sites are discussed.

EAE mouse model of human multiple sclerosis, C57BL/6 mice, Immunization mice with myelin oligodendrocyte glycoprotein (MOG) and DNA-histones complex, Catalytic IgGs, Hydrolysis of histones and myelin basic protein, Cross-complexation and catalytic cross-reactivity