Antibodies to myelin lipids in multiple sclerosis

Cover Page

Abstract

Development of immunopathological reactions in the central nervous system (CNS) is one of the key events in the pathogenesis of multiple sclerosis (MS). Humoral immune responses with formation of antibodies to the components of the myelin sheath play an important role. However, the targets for antibodies, their contribution to the development of pathologic process, and stages of the disease, where they play the most important role, are still not quite clear. In this study, we investigated the frequency of detection of antibodies to myelin glycolipids in MS and their relationship with clinical features of the disease. The results of the study showed that patients with MS demonstrate a trend towards more frequent detection of antibodies to glycolipids and sulfatide in blood serum, which is especially pronounced in patients with secondary progressive course. Antibodies to GM1 ganglioside were significantly more frequently detected in patients with secondary progressive MS as compared to patients with remitting course and healthy volunteers. These results are indicative of the fact that antibodies to lipids may participate in the development of demyelinating and neurodegenerative processes in MS and be the markers of disease progression. Further development of the concept of the mechanisms of humoral response to myelin lipids in MS and identification of the most significant antibody targets will facilitate the development of new approaches to prediction of disease course and discovery of new targets for immunomodulating therapy.

About the authors

M. V. Ivanova

Research Center of Neurology (Moscow)

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

M. N. Zakharova

Research Center of Neurology (Moscow)

Email: platonova@neurology.ru
Russian Federation

References

  1. Калашникова Л.А. Цереброваскулярные нарушения при антифосфолипидном синдроме. Анн. клин. и эксперим. неврол. 2011;1: 39–43.
  2. Супонева Н.А., Пирадов М.А., Никитин С.С. и др. Патогенетическая и проностическая роль аутоантител к ганглиозидам периферических нервов при синдроме Гийена–Барре. Анн. клин. и эксперим. неврол. 2013; 1: 4–11.
  3. Alpa M., Ferrero B., Cavallo R. et al. Anti-GM1 and anti-sulfatide antibodies in patients with systemic lupus erythematosus, Sjögren’s syndrome, mixed cryoglobulinemia and idiopathic systemic vasculitis.Clin. Experiment. Rheumatol. 2007; 25: 556–62.
  4. Álvarez-Cermeño J.C., Muñoz-Negrete F.J., Costa-Frossard L. et al. Intrathecal lipid-specific oligoclonal IgM synthesis associates with retinal axonal loss in multiple sclerosis. J. Neurol. Sci. 2016; 360: 41–44.
  5. Andersson K., Buschard K., Fredman P. et al. Patients with insulindependent diabetes but not those with non-insulin-dependent diabetes have anti-sulfatide antibodies as determined with a new ELISA assay. Autoimmunity. 2002; 35: 463–468.
  6. Brennan K.M., Galban-Horcajo F., Rinaldi S. et al. Lipid arrays identify myelin-derived lipids and lipid complexes as prominent targets for oligoclonal band antibodies in multiple sclerosis. J. Neuroimmunol.2011; 238: 87–95.
  7. Caudie C., Pinon A.Q., Bouhour F. et al. Comparison of commercial tests for detecting multiple anti-ganglioside autoantibodies in patients with well-characterized immune-mediated peripheral neuropathies. Clin. Labor. 2014; 59: 1277–1287.
  8. Fernández-Menéndez S., Fernández-Morán M., Fernández-Vega I. et al. Epstein-Barr virus and multiple sclerosis. From evidence to therapeutic strategies. J. Neurol. Sci. 2016; 361: 213–219.
  9. Giovannoni G., Morris P.R., Keir G. Circulating antiganglioside antibodies are not associated with the development of progressive disease or cerebral atrophy in patients with multiple sclerosis. Ann. Neurol. 2000; 47: 684–685.
  10. Gold M., Pul R., Bach J.P. et al. Pathogenic and physiological autoantibodies in the central nervous system. Immunol. Rev. 2012; 248: 68–86.
  11. Haghighi S., Lekman A., Nilsson S. et al. Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis. Acta Neurol. Scand. 2012; 125: 64–70.
  12. Haghighi S., Lekman A., Nilsson S. et al. Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients. J. Neurol. Sci. 2013; 326: 35–39.
  13. Ilyas A.A., Chen Z.W., Cook S.D. Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J. Neuroimmunol. 2003;139: 76–80.
  14. Joseph F.G., Hirst C.L., Pickersgill T.P. et al. CSF oligoclonal band status informs prognosis in multiple sclerosis: A case control study of 100 patients. J. Neurol. Neurosurg. Psychiatry 2009; 80: 292–296.
  15. Kakalacheva K., Münz C., Lünemann J.D. Viral triggers of multiple sclerosis. Biochim. Biophys. Acta. 2011; 1812: 132–140.
  16. Kanter J.L., Narayana S., Ho P.P. et al. Lipid microarrays identify key mediators of futoimmune brain inflammation. Nat. Med. 2006; 12:138–143.
  17. Kusunoki S.R., Yu K., Kim J.H. Induction of experimental autoimmune encephalomyelitis in guinea pigs using myelin basic protein and myelin glycolipids. J. Neuroimmunol. 1988; 18: 303–314.
  18. Magraner M.J., Bosca I., Simó-Castelló M. et al. Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes. Neuroradiology. 2012; 54: 5–12.
  19. Mullin B.R., Decandis F.X., Montanaro A.J., Reid J.D. Myelin basic protein interacts with the myelin-specific ganglioside GM4. Brain Res.1981; 222: 218–221.
  20. Sadatipour B.T., Greer J.M., Pender M.P. Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann. Neurol. 1998; 44: 980–983.
  21. Walsh M.J., Tourtellotte W.W. Temporal invariance and clonal uniformity of brain and cerebrospinal IgG, IgA, and IgM in multiple sclerosis. J. Experiment. Med. 1986; 163: 41–53.
  22. Zaprianova E., Majtényi K., Deleva D. et al. Serum IgG and IgM Ganglioside GM1 antibodies in patients with multiple sclerosis. Ideggyógyászati Szemle. 2004; 57: 94–99.

Statistics

Views

Abstract: 945

PDF (Russian): 1926

Article Metrics

Metrics Loading ...

Dimensions

PlumX


Copyright (c) 2017 Ivanova M.V., Zakharova M.N.

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

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies