Association of BAFF gene polymorphisms with multiple sclerosis progression
https://doi.org/10.14412/2074-2711-2020-1-22-26
Abstract
The cytokine of the tumor necrosis factor (TNF) family B-cell activating factor (BAFF) (TNFSF13B) that regulates the proliferation, differentiation, and survival of B cells is assumed to be involved in the pathogenesis of multiple sclerosis (MS).
Objective: to analyze the association of BAFF gene polymorphisms (rs1224141, rs9514827) with the progression rate and frequency of MS exacerbations.
Patients and methods. A total of 100 Caucasian patients (24 males and 76 females) with relapsing-remitting MS, who were born and lived in the Altai Territory of the Russian Federation, were examined. Genotyping was performed by real-time polymerase chain reaction using competitive TaqMan probes.
Results and discussion. The annual risk of a>0.75 point disability increase in the Expanded Disability Status Scale (EDSS) score was ascertained to be associated with the first remission duration of less than 2 years, with the G/G genotype of BAFF (rs1224141) in males and females, and with the C/C genotype of BAFF (rs9514827) in females. The likelihood of the first remission duration of less than 2 years was increased in female carriers of the G allele of BAFF (rs1224141). There was no association of BAFF gene polymorphisms (rs1224141, rs9514827) with the frequency of MS exacerbations.
It seems promising to further study the role of BAFF in the pathogenesis of MS and the effect of this cytokine on the specific features of the course of the disease. The investigation results will be able to predict the efficiency of MS therapy with anti-BAFF drugs and to identify criteria for their individualized use.
Conclusion. In patients with MS in the Altai Territory of the Russian Federation, the risk for a high MS progression rate is related to the carriage of BAFF genotypes with rare alleles in homozygous state: G/G polymorphism rs1224141, C/C polymorphism rs9514827 in combination with the female sex. The G allele of BAFF (rs1224141) in women is associated with the risk of the unfavorable prognostic duration of the first MS remission of less than 24 months.
Objective: to analyze the association of BAFF gene polymorphisms (rs1224141, rs9514827) with the progression rate and frequency of MS exacerbations.
Patients and methods. A total of 100 Caucasian patients (24 males and 76 females) with relapsing-remitting MS, who were born and lived in the Altai Territory of the Russian Federation, were examined. Genotyping was performed by real-time polymerase chain reaction using competitive TaqMan probes.
Results and discussion. The annual risk of a>0.75 point disability increase in the Expanded Disability Status Scale (EDSS) score was ascertained to be associated with the first remission duration of less than 2 years, with the G/G genotype of BAFF (rs1224141) in males and females, and with the C/C genotype of BAFF (rs9514827) in females. The likelihood of the first remission duration of less than 2 years was increased in female carriers of the G allele of BAFF (rs1224141). There was no association of BAFF gene polymorphisms (rs1224141, rs9514827) with the frequency of MS exacerbations.
It seems promising to further study the role of BAFF in the pathogenesis of MS and the effect of this cytokine on the specific features of the course of the disease. The investigation results will be able to predict the efficiency of MS therapy with anti-BAFF drugs and to identify criteria for their individualized use.
Conclusion. In patients with MS in the Altai Territory of the Russian Federation, the risk for a high MS progression rate is related to the carriage of BAFF genotypes with rare alleles in homozygous state: G/G polymorphism rs1224141, C/C polymorphism rs9514827 in combination with the female sex. The G allele of BAFF (rs1224141) in women is associated with the risk of the unfavorable prognostic duration of the first MS remission of less than 24 months.
About the Authors
I. V. Smagina
Altai State Medical University, Ministry of Health of Russia;
Territorial Clinical Hospital
Russian Federation
Russian Federation
40, Lenin Prosp., Barnaul 656038
1, Lyapidevsky St., Barnaul 656024
S. A. Elchaninova
Altai State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
40, Lenin Prosp., Barnaul 656038
A. S. Palashchenko
Altai State Medical University, Ministry of Health of Russia;
Territorial Clinical Hospital
Russian Federation
Russian Federation
40, Lenin Prosp., Barnaul 656038
1, Lyapidevsky St., Barnaul 656024
References
1. Gusev EI, Zavalishin IA, Boiko AN. Rasseyannyi skleroz. Klinicheskoe rukovodstvo [Multiple sclerosis. Clinical guidance]. Moscow: Peal Taim; 2011. 528 p.
2. Bеdri SK, Fink K, Mаnоuсhеhriniа А, et al. Multiрlе sсlеrоsis trеаtmеnt еffесts оn рlаsmа сytоkinе rесерtоr lеvеls. Clin Immunol. 2018 Feb;187:15-25. doi: 10.1016/j.clim.2017.08.023. Epub 2017 Sep 21.
3. International Multiple Sclerosis Genetics Consortium; Beecham AH, Patsopoulos NA, Xifara DK, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013 Nov; 45(11):1353-60. doi: 10.1038/ng.2770. Epub 2013 Sep 29.
4. Palle P, Monaghan KL, Milne SM, Wan Edwin CK. Сytоkinе signаling in multiрlе sсlеrоsis аnd its thеrареutiс аррliсаtiоns. Med Sci (Basel). 2017 Oct 13;5(4). pii: E0023. doi: 10.3390/medsci5040023.
5. Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev. 2011 Nov;244(1):115-33. doi: 10.1111/j.1600-065X.2011.01067.x.
6. Rahmanzadeh R, Weber MS, Brü ck W, et al. B cells in multiple sclerosistherapy A comprehensive review. Acta Neurol Scand. 2018 Jun; 137(6):544-556. doi: 10.1111/ane.12915. Epub 2018 Mar 7.
7. Marin-Rosales M, Cruz A, Salazar-Camarena DC, et al. High BAFF expression associated with active disease in systemic lupus erythematosus and relationship with rs9514828C>T polymorphism in TNFSF13B gene. Clin Exp Med. 2019 May;19(2):183-190. doi: 10.1007/s10238-019-00549-8. Epub 2019 Feb 11.
8. Nezos A, Papageorgiou A, Fragoulis G, et al. B-cell activating factor genetic variants in lymphomagenesis associated with primary Sjogren's syndrome. J Autoimmun. 2014 Jun;51:89-98. doi: 10.1016/j.jaut.2013.04.005. Epub 2013 Jul 9.
9. Steri M, Orru V, Idda ML, et al. Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med. 2017 Apr 27; 376(17):1615-1626. doi: 10.1056/NEJMoa1610528.
10. Gonza’lez-Serna D, Carmona EG, Ortego-Centeno N, et al. A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility. PLoS One. 2018 Dec 26;13(12):e0209343. doi: 10.1371/journal.pone.0209343. eCollection 2018.
11. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.
12. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11): 1444-52.
13. Malkova NA, Ierusalimskii AP. Rasseyannyi skleroz [Multiрlе sсlеrоsis]. Novosibirsk; 2006. 198 p.
14. Smagina IV, El'chaninova SA, Zolovkina AG, Gridina AO. Factors associated with high rate of multiple sclerosis progression. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;111(2-2):25-9. (In Russ.).
15. Sonar S, Lal G. Role of tumor necrosis factor superfamily in neuroinflammation and autoimmunity. Front Immunol. 2015 Jul 20; 6:364. doi: 10.3389/fimmu.2015.00364. eCollection 2015.
16. Kannel K, Alnek K, Vahter L, et al. Changes in Blood B Cell Activating Factor (BAFF) Levels in Multiple Sclerosis: A Sign of Treatment Outcome. PLoS One. 2015 Nov 23; 10(11):e0143393. doi: 10.1371/journal.pone.0143393. eCollection 2015.
17. Baker D, Marta M, Pryce G, et al. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. E BioMedicine. 2017 Feb;16:41-50. doi: 10.1016/j.ebiom.2017.01.042. Epub 2017 Jan 31.
18. Ragheb S, Li Y, Simon K, et al. Multiple sclerosis: BAFF and CXCL13 in cerebrospinal fluid. Mult Scler. 2011 Jul;17(7):819-29. doi: 10.1177/1352458511398887. Epub 2011 Mar 3.
19. Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med. 2005 Jan 17;201(2):195-200. Epub 2005 Jan 10.
Review
For citations:
Smagina I.V., Elchaninova S.A., Palashchenko A.S. Association of BAFF gene polymorphisms with multiple sclerosis progression. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(1):22-26. https://doi.org/10.14412/2074-2711-2020-1-22-26
Views: 442
Email this article 