Ukr.Biochem.J. 2020; Volume 92, Issue 6, Nov-Dec, pp. 77-84


Autoantibodies to myelin basic protein and histone H1 as immune biomarkers of neuropsychological disorders in patients with multiple sclerosis

S. Ya. Kyryliuk1, T. I. Nehrych1, N. K. Svyrydova2,
Ye. O. Trufanov2, R. S. Stoika3, Yu. Ya. Kit3

1Danylo Halytsky Lviv National Medical University, Ukraine;
2Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine;
3Institute of Cell Biology National Academy of Sciences of Ukraine, Lviv;

Received: 15 April 2020; Accepted: 13 November 2020

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with different disorders of neurological and higher cortical functions. It is important to identify biomarkers that can control the dynamics of neuropsychological changes and predict the progression of this process. The aim of the study was to investigate the pathogenic and clinical significance of serum autoantibodies to the myelin basic protein (MBP) and histone H1 in the occurrence of neurological and neuropsychological disorders in patients with MS. Fifty-five patients diagnosed for MS were examined. A general clinical and neurological examination, determination of cognitive status, depression level and the content of autoantibodies to histone H1 and MBP in the blood serum were conducted. Blood serum samples of 20 healthy volunteers were used in control.  The serum of patients with MS was shown to contain antibodies of IgG class to MBP and histone H1. The level of anti-histone H1 IgG-antibodies in blood serum of MS patients was found to be higher compared with the level of anti-MBP IgG-antibodies (P < 0.05). Increased levels of anti-MBP antibodies correlated with the severity of trunk ataxia, impaired conceptualization, and mood. High level of anti-histone H1 antibodies correlated with the severity of paresis, trunk ataxia, impaired conceptualization, semantic language, and mood. Determination of the level of anti-histone H1 antibodies in blood serum of patients with MS might serve as a biomarker of inflammatory and, probably, of the neurodegenerative processes of this disease and determine the dynamics of clinical course of the MS. Anti-MBP antibodies play an important role in the pathogenesis of the MS and are an additional marker of the severity of the clinical course of neurological and some neuropsychological disorders.

Keywords: , , , , ,


  1. Antonyuk Т. Multiple sclerosis: situational analysis of the problem in Ukraine. Neuronews. 2018; 3(96): 6-9. (In Ukrainian).
  2. Oh J, Vidal-Jordana A, Montalban X. Multiple sclerosis: clinical aspects. Curr Opin Neurol. 2018;31(6):752-759. PubMed, CrossRef
  3. Negrych NO, Nehrych TI. Algorithm of using a set of laboratory biomarkers in patients with multiple sclerosis with diagnostic and prognostic aim. Int Neurol J. 2018;(3(97)): 27-35. (In Ukrainian).  CrossRef
  4. Buchakchijska NM, Demchenko AV. Cognitive impairment in patients with multiple sclerosis. Int Neurol J. 2007;11(1): 36-41. (In Ukrainian).
  5. Kyrylyuk SYa. Cognitive impairment in patients with multiple sclerosis and their dependence on social and demographic factors. Ukr Nevrol Zhurn. 2015;(1(34)): 56-65. (In Ukrainian).
  6. Benedict RHB, DeLuca J, Enzinger C, Geurts JJG, Krupp LB, Rao SM. Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward. J Int Neuropsychol Soc. 2017;23(9-10):832-842. PubMed, CrossRef
  7. Chiaravalotti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;(12): 1139-1151. PubMed, CrossRef
  8. Grzegorski T, Losy J. Cognitive impairment in multiple sclerosis – a review of current knowledge and recent research. Rev Neurosci. 2017;28(8):845-860. PubMed, CrossRef
  9. Patten SB, Marrie RA, Carta MG. Depression in multiple sclerosis. Int Rev Psychiatry. 2017;29(5):463-472. PubMed, CrossRef
  10. Hedegaard CJ, Chen N, Sellebjerg F, Sørensen PS, Leslie RG, Bendtzen K, Nielsen CH. Autoantibodies to myelin basic protein (MBP) in healthy individuals and in patients with multiple sclerosis: a role in regulating cytokine responses to MBP. Immunology. 2009;128(1 Suppl):e451-e461.
    PubMed, PubMedCentral, CrossRef
  11. Mallucci G, Peruzzotti-Jametti L, Bernstock JD, Pluchino S. The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis. Prog Neurobiol. 2015;127-128:1-22. PubMed, PubMedCentral, CrossRef
  12. Kyryliuk SYa, Nehrych TI, Stoika RS, Кit YuYa. Autoantibodies class IgG to myelin basic protein and histone H1 as new biological markers of multiple sclerosis. Int Neurol J. 2014;(5(67)): 19-26. (In Ukrainian).
  13. Ferec C, Youinou P, Le Goff P, Miossec P, Morin JF, Pennec Y, Morin PP, Le Menn G. Significance of antinuclear anti-histone antibodies. Ann Med Interne (Paris). 1984;135(6):427-430. PubMed
  14. Kit YuYa, Starykovych MA, Richter VA, Stoika RS.Detection and characterization of IgG- and sIgA-Abzymes capable of hydrolyzing histone H1. Biochemistry (Mosc). 2008;73(8):950-956. PubMed, CrossRef
  15. Mishra B, von der Ohe M, Schulze C, Bian S, Makhina T, Loers G, Kleene R, Schachner M. Functional role of the interaction between polysialic acid and extracellular histone H1. J Neurosci. 2010;30(37):12400-12413. PubMed, PubMedCentral, CrossRef
  16. Roque A Ponte I, Suau P. Interplay between histone H1 structure and function. Biochim Biophys Acta. 2016;1859(3):444-454. PubMedCrossRef
  17. Gilthorpe JD, Oozeer F, Nash J, Calvo M, Bennett DL, Lumsden A, Pini A. Extracellular histone H1 is neurotoxic and drives a pro-inflammatory response in microglia. F1000Res. 2013;2:148.  PubMed, PubMedCentral, CrossRef
  18. Nakano T, Kamei R, Fujimura T, Takaoka Y, Hori A, Lai CY, Chiang KC, Shimada Y, Ohmori N, Goto T, Ono K, Chen CL, Goto S, Kawamoto S. Impact of histone H1 on the progression of allergic rhinitis and its suppression by neutralizing antibody in mice. PLoS One. 2016;11(4):e0153630. PubMed, PubMedCentral, CrossRef
  19. Stummvoll GH, Fritsch RD, Meyer B, Hoefler E, Aringer M, Smolen JS, Steiner G. Characterisation of cellular and humoral autoimmune responses to histone H1 and core histones in human systemic lupus erythaematosus. Ann Rheum Dis. 2009;68(1):110-116. PubMed, CrossRef
  20. Kyryliuk SYa, Nehrych TI, Stoika RS, Кit YuYa. Value of autoantibodies to myelin basic protein and histone H1 in the pathogenesis of neuropsychological disorders in patients with multiple sclerosis. Ukr Nevrol Zhurn. 2014;(3-4): 48-54.
  21. Chamczuk AJ, Ursell M, O’Connor P, Jackowski G, Moscarello MA. A rapid ELISA-based serum assay for myelin basic protein in multiple sclerosis. J Immunol Methods. 2002;262(1-2):21-27. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.