Modern aspects of B lymphocytes in the pathogenesis of multiple sclerosis: the use of B-cell biomarkers in clinical practice

N.O. Negrych, S.L. Myronovskij, T.I. Nehrych, Yu.Ya. Kit, R.S. Stoika

Abstract


Background. The purpose was to investigate the correlation between the level of 48 kDa form of unconventional myosin 1c (48 kDa Myo1c) (marker of apoptosis in cells) in the blood serum of patients with multiple sclerosis (MS), and features of the disease debut in the context of the modern understanding of the key role of B lymphocytes even at the early stage of pathological process in MS. Materials and methods. 61 patients with multiple sclerosis and 20 healthy donors aged 19–57 years participated in the research. Methods of investigation: clinical (complaints, life and disease history, general and neurological examination), laboratory (identification of 48 kDa Myo1c in the blood serum by consequent serum protein sedimentation, electrophoresis and digital analysis of electrophoregrams; presence of Myo1c was confirmed by Western blot with anti-Myo1c antibodies). Results. In the group of MS patients with high level of 48 kDa Myo1c, the average age of the patients at the time of disease onset was the lowest, but significant statistical relationships between concentrations of 48 kDa Myo1c in the serum of patients and age of MS debut were not found.
At the onset of MS as a reduction of visual acuity, the average level of 48 kDa Myo1c in the blood serum of patients was revealed significantly more often, and at the onset of oculomotor disorders — a low level, indicating a less favorable course of the disease due to the low apoptosis of autoreactive lymphocytes. Levels of serum 48 kDa Myo1c were not significantly dependent on the disease activity in MS patients at the time of examination and blood sampling, and therefore the use of this biomarker is possible not only during the exacerbation of the disease, but also during remission. Conclusions. Modern researches show that in MS B lymphocytes are involved not only in the synthesis of oligoclonal autoantibodies, but also in the antibody-independent mechanisms, especially in the presentation of antigens to T cells, synthesis of pro-inflammatory cytokines, the formation of ectopic lymphoid follicle-like clusters in the central nervous system. Therefore, it is a reasonable to use B cell markers, including 48 kDa Myo1c, in clinical practice, particularly, to predict the course of MS aggressiveness and effectiveness of disease-modifying therapies.


Keywords


multiple sclerosis; B cells; biomarkers; unconventional myosin

References


Lassmann H., Brück W., Lucchinetti C.F. The immunopathology of multiple sclerosis: an overview // BrainPathol. — 2007. — Vol. 17. — P. 210-8. doi:10.1111/j.1750-3639.2007.00064.x.

Соколова Л.И. К вопросу о современных методах диагностики и лечения рассеянного склероза // Мед. вестник. — 2008. — № 1. — С. 28-32.

Евтушенко С.К., Москаленко М.А. Рассеянный склероз у детей. — К., 2009. — 385 с.

Волошина Н.П., Левченко І.Л. Фармакоекономічне обґрунтування патогенетичного лікування розсіяного склерозу // Міжнародний неврологічний журнал. — 2006. — № 4. — С. 91-98.

Weiner H.L. Multiple sclerosisis an inflammatory T-cell-mediated autoimmune disease // Archives of Neurology. — 2004. — Vol. 61(10). — P. 1613-1615. doi:10.1001/archneur.61.10.1613.

O’Brien K., Gran B., Rostami A. T-cell based immunotherapy in experimental autoimmune encephalomyelitis and multiples clerosis // Immunotherapy. — 2010. — Vol. 2(1). — P. 99-115.

Disanto G., Morahan J.M., Barnett M.H., Giovannoni G., Ramagopalan S.V. The evidence for a role of B cells in multiple sclerosis // Neurology. — 2012. — Vol. 78(11). — P. 823-832. doi:10.1212/WNL.0b013e318249f6f0.

Miljković D., Spasojevic I. Multiple Sclerosis: Molecular Me­chanisms and Therapeutic Opportunities // Antioxid Redox Signal. — 2013. — Vol. 19(18). — P. 2286-334. doi:10.1089/ars.2012.5068.

Шоробура М.С., Негрич Т.І., Стойка Р.С. Здатність імуноглобулінів сироватки крові хворих на розсіяний склероз різного віку (діти й дорослі особи) впливати на імунокомпетентні клітини // Міжнародний неврологічний журнал. — 2008. — Т. 2(18).

Villar L.M., Masterman T., Casanova B., Gómez-Rial J., Espiño M., Sádaba M.C. et al. CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis // J. Neuroimmunol. — 2009. — Vol. 211. — P. 101-4. doi:10.1016/j.jneuroim.2009.03.003.

Dobson R., Ramagopalan S., Davis A., Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude // J. Neurol. Neurosurg. Psychiatry. — 2013. — Vol. 84. — P. 909-14. doi:10.1136/jnnp-2012-304695.

Meinl E., Krumbholz M., Hohlfeld R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation // Ann. Neurol. — 2006. — Vol. 59. — P. 880-92. doi:10.1002/ana.20890.

Polman C.H., Reingold S.C., Banwell B. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria // Ann. Neurol. — 2011. — Vol. 69(2). — P. 292-302. doi:10.1002/ana.22366.

Franciotta D., Salvetti M., Lolli F., Serafini B., Aloisi F. B cells and multiple sclerosis // The Lancet Neurology. — 2008. — Vol. 7(9). — P. 852-858. doi:10.1016/S1474-4422(08)70192-3.

Link H., Huang Y.M. Oligoclonal bands in multiples clerosis cerebrospinal fluid: an update on methodology and clinical usefulness // Journal of neuroimmunology. — 2006. — Vol. 180(1). — P. 17-28. doi:10.1016/j.jneuroim.2006.07.006.

Ireland S.J., Blazek M., Harp C.T., Greenberg B., Froh­man E.M., Davis L.S., Monson N.L. Antibody-independent B cell effector functions in relapsing remitting multiple sclerosis: clues to increased inflammatory and reduced regulatory B cell capacity // Autoimmunity. — 2012. — Vol. 45(5). — P. 400-414. doi:10.3109/08916934.2012.665529.

Lisak R.P., Benjamins J.A., Nedelkoska L., Barger J.L., Ragheb S., Fan B., Bar-Or A. Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro // Journal of neuroimmunology. — 2012. — Vol. 246(1). — P. 85-95. doi:10.1016/j.jneuroim.2012.02.015.

Magliozzi R., Howell O.W., Reeves C., Roncaroli F., Nicholas R., Serafini B. et al. A Gradient of neuronal loss and meningeal inflammation in multiples clerosis // Annals of neurology. — 2010. — Vol. 68(4). — P. 477-493. doi:10.1002/ana.22230.

Howell O.W., Reeves C.A., Nicholas R., Carassiti D., Radotra B.,

Gentleman S.M. et al. Meningeal inflammation is wide spread and linked to cortical pathology inmultiple sclerosis // Brain. — 2011. — Vol. 134(9). — P. 2755-2771. doi:10.1093/brain/awr182.

Myronovkij S., Negrych N., Nehrych T. et al. Identification of a 48 kDa form of unconventional myosin 1c in blood serum of patients with autoimmune diseases // Biochemistry and Biophysics Reports. — 2016. — Vol. 5. — P. 175-179. doi:10.1016/j.bbrep.2015.12.001.

Maravillas-Montero J., Gillespie P., Patiño-López G. at al. Myosin 1c participates in B cell cytoskeleton rearrangements, isrecruited to the immunologic synapse, and contributes to antigen presentation // J. Immunol. — 2011. — Vol. 187(6). — P. 3053-3063. doi:10.4049/jimmunol.1004018.

Cencioni M.T., Santini S., Ruocco G. et al. FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients // Cell Death and Disease. — 2015. — Vol. 6. — P. e1741. doi:10.1038/cddis.2015.100.

Kurtzke J.F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) // Neurology. — 1983. — Vol. 33 (11). — P. 1444-52. doi:10.1212/WNL.33.11.1444.

Confavreux C., Vukusic S. The clinical course of multiple sclerosis // Handbook of Clinical Neurology. — 2014. — Vol. 122. — P. 343-369. doi:10.1016/B978-0-444-52001-2.00014-5.

Housley W.J., Pitt D., Hafler D.A. Biomarkers in multiples clerosis // Clinical Immunology. — 2015. — Vol. 161(1). — P. 51-58. doi:10.1016/j.clim.2015.06.015.

Frischer J.M., Bramow S., Dal-Bianco A. et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains // Brain. — 2009. — Vol. 132(5). — P. 1175-1189. doi:10.1093/brain/awp070.

Dalakas MC. B cells as therapeutic targets in autoimmune neurological disorders // Nature Clinical Practice Neurology. — 2008. — Vol. 4(10). — P. 557-567. doi:10.1038/ncpneuro0901.

Montalban X., Hauser S.L., Kappos L., Lapierre Y., O’Connor P., Devonshire V. et al. Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis // N. Engl. J. Med. — 2017. — Vol. 376. — P. 1692-1694. doi:10.1056/NEJMc1702076.




DOI: https://doi.org/10.22141/2224-0713.3.89.2017.104241

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 INTERNATIONAL NEUROLOGICAL JOURNAL

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

 

© Publishing House Zaslavsky, 1997-2017

 

 Яндекс.МетрикаSeo анализ сайта Рейтинг@Mail.ru