Dynamics of immune status indicators in patients with relapsing-remitting multiple sclerosis before and after treatment of Betfer-1a drug

Authors

  • N Vdovichenko Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України", Ukraine
  • T Kolyada Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України", Ukraine
  • O Tupotilov Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України",
  • T. Negreba Інститут неврології, психіатрії та наркології НАМН України,
  • O. Kolyada Харківський національний медичний університет,

Keywords:

multiple sclerosis, IFN-β, immune status, disease-associated gene polymorphism

Abstract

The article presents the results of examination of 58 patients with relapsing-remitting multiple sclerosis (RRMS) treated IFN-β. Depending on the effectiveness of treatment, patients were divided into two groups: responders, included 37 persons (64%), in this group patients did not relapse during the year from the beginning of treatment, the degree of EDSS remained unchanged or decreased, the group EDSS before the start of therapy was 2.2 ± 1.4 points. After therapy, EDSS was 2.1 ± 1.4 points.- non-responders, this group included 21 individuals, the patient was included in the group if he had at least one relapse during the year and / or an increase in the degree of disability on the EDSS was found to be 1 point or more. The group EDSS before the start of therapy was 2.5 ± 1.5 points. After therapy, EDSS was 3.0 ± 1.5 points. The immunological characteristics of the patients are presented, depending on the clinical efficacy of the treatment; the presence of disease-associated polymorphic variants of HLA-DR has been determined. After the course of therapy with IFN-β, in patients with RRMS, regardless of the clinical efficacy of treatment, the relative number of T-lymphocytes and natural killer cells remained significantly reduced. In the group of responders levels of circulating immune complexes and IgG levels did not differ from control after treatment, in contrast to the levels of lymphocytotoxic autoantibodies and complement activity, which remained elevated relative to the control. After treatment in patients with low efficacy of IFN-β therapy (nonresponders), the relative number of CD19+ cells, as well as the levels of IgG, circulating immune complexes and lymphocytotoxic autoantibodies remained elevated relative to the control group. The presence of the haplotype HLA-DRB1*1501-DQB1*0602 (one of its specific markers is allele G SNP rs9271366) is established to determine the association between the disease-associated polymorphism of HLA-DR and the effectiveness of IFN-β therapy. The presence of the minor disease-associated G allele was determined in 11 responders (29.7%) (heterozygous), another 26 patients (70.3%) were homozygous for major allele A. In the group of non-responders, 9 persons (42, 9%) were heterozygous, 12 (57.1%) were homozygous for major allele A.

Author Biographies

N Vdovichenko, Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України"

науковий співробітник лабораторії клінічної імунології та алергології

T Kolyada, Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України"

Завідувачка лабораторії клінічної імунології та алергології

O Tupotilov, Державна установа "Інститут мікробіології та імунології ім. І. І. Мечникова НАМН України"

молоддший науковий співробітник лабораторії клінічної імунології та алергології

T. Negreba, Інститут неврології, психіатрії та наркології НАМН України

провідний науковий співробітник відділу нейроінфекцій та розсіяного склерозу

O. Kolyada, Харківський національний медичний університет

асистент кафедри патологічної фізіології ХНМУ

References

Rudick R.A., Lee J.C., Simon J., et al. Defining interferon beta response status in multiple sclerosis patients. Ann Neurol. 2004. V 56. P.548–555

Lill C. M. Recent advances and future challenges in the genetics of multiple sclerosis. Front. Neurol. 2014. N 5: 130. URL: http://dx.doi.org/10.3389/fneur.2014.00130

Наказ МОЗ України №487 від 17.08.2007 р. «Про затвердження клінічних протоколів надання медичної допомоги за спеціальністю «Неврологія»». Київ. 2007

Hegen H., Auer M., Deisenhammer F. Predictors of response to multiple sclerosis therapeutics in individual patients. Drugs. 2016. 76: 1421

Frolov V.M., Rychnev V. Е. Investigation of circulating immune complexes: diagnostic and prognostic value. Laboratory work.1986. 3. 159-16

Reznikova L.S. Complement and its Importance in Immunological Reactions. Moscow: Medicine,1967

Liu, Jing et al. An Improved Allele-Specific PCR Primer Design Method for SNP Marker Analysis and Its Application. Plant Methods. 2015. 8. 34. PMC.

Vališ M, Vyšata O, Sobíšek L, Klímová B, Andrýs C, Vokurková D, et al. Monitoring of lymphocyte populations during treatment with Interferon-b-1b to predict multiple sclerosis disability progression. Journal of interferon & cytokine research. 2019. 39(3). P. 164-173.

doi: 10.1089/jir.2018.0100.

Miranda-Hernandez S, Baxter AG. Role of toll-like receptors in multiple sclerosis. American journal of clin. and experim. immunol. 2013. 2(1). P. 75-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714200

Hedström A. K., Bomfim I. L., Barcellos L. F. et al] Interaction between passive smoking and two HLA geneswith regard tomultiple sclerosis risk // Int. J. Epidemiol. 2014. Vol. 43. P. 1791–1798. http://dx.doi.org/10.1093/ije/dyu195

Link J., Lundkvist R. M., Fink K. et al. Human leukocyte antigen genes and interferon beta preparations influence risk of developing neutralizing anti-drug antibodies in multiple sclerosis. PLoS One. 2014. 9(3). e90479. doi:10.1371/journal.pone.0090479

George M. F., Briggs B. S., Shao X. et al Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies. Neurology: Genetics. 2016. Vol. 2 (4). e87. http://doi.org/10.1212/NXG.0000000000000087

Published

2019-09-30

How to Cite

Vdovichenko, N., Kolyada, T., Tupotilov, O., Negreba, T., & Kolyada, O. (2019). Dynamics of immune status indicators in patients with relapsing-remitting multiple sclerosis before and after treatment of Betfer-1a drug. Annals of Mechnikov’s Institute, (3), 30–34. Retrieved from https://journals.uran.ua/ami/article/view/185586

Issue

Section

Research Articles