Impact of cytomegalovirus infection on B cell differentiation and cytokine production in multiple sclerosis
Zabalza, Ana (Institut Hospital del Mar d'Investigacions Mèdiques)
Vera, Andrea (Institut Hospital del Mar d'Investigacions Mèdiques)
Alari Pahissa, Elisenda (Universitat Pompeu Fabra)
Munteis, Elvira (Institut Hospital del Mar d'Investigacions Mèdiques)
Moreira Villanueva, Antía (Althaia Xarxa Assistencial Universitària de Manresa)
Yélamos, José (Institut Hospital del Mar d'Investigacions Mèdiques)
Llop, Mireia (Institut Hospital del Mar d'Investigacions Mèdiques)
López-Botet, Miguel (Institut Hospital del Mar d'Investigacions Mèdiques)
Martinez Rodriguez, Jose Enrique (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2020
Resum:	Human cytomegalovirus (HCMV) infection has been recently associated with a low risk of multiple sclerosis (MS), yet the basis behind this observation remains uncertain. In this study, we aimed to determine in MS patients whether HCMV induces modifications in the peripheral B cell compartment. HCMV serostatus was determined in 73 MS patients (55 relapsing-remitting MS (RRMS); 18 progressive MS (PMS)) and 30 healthy controls, assessing their B cell immunophenotype and cytokine production (GM-CSF, IL-6, IL-10, and TNFα) by flow cytometry. HCMV seropositivity in untreated MS patients (n = 45) was associated with reduced switched memory B cells, contrasting with an opposite effect in PMS. Expansions of transitional B cells were observed in HCMV(+) IFNβ-treated RRMS patients but not in HCMV(-) cases (p < 0. 01), suggesting that HCMV may influence the distribution of B cell subsets modulating the effects of IFNβ. Considering the B cell functional profile, HCMV(-) PMS displayed an increased secretion of proinflammatory cytokines (IL-6, TNFα) as compared to HCMV(+) PMS and RRMS cases (p < 0. 001). Our study reveals an influence of HCMV infection on the phenotype and function of B cells, promoting early differentiation stages in RRMS and reducing the proinflammatory cytokine profile in advanced MS forms, which might be related with the putative protective role of this virus in MS.
Ajuts:	Ministerio de Economía y Competitividad FIS/PI17/00254 Agencia Estatal de Investigación SAF2016-80363-C2-1-R Ministerio de Economía y Competitividad PCIN-2015-191-C02-01
Nota:	Altres ajuts: This work was supported by the EU FP7-MINECO Infect-ERA Program, and Red Española de Esclerosis Múltiple (REEM) from the Instituto de Salud Carlos III, the European Regional Development Fund (Grant RD16/0015/0011), and the Spanish Ministry of Economy and Competitiveness.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Multiple sclerosis ; B cells ; Human cytomegalovirus ; Interferon-beta
Publicat a:	Journal of neuroinflammation, Vol. 17 (may 2020) , ISSN 1742-2094

DOI: 10.1186/s12974-020-01840-2
PMID: 32434524

8 p, 2.1 MB

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