Abstract
BackgroundHuman 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.MethodsHCMV 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.ResultsHCMV 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).ConclusionsOur 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.
Highlights
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system classically considered to be mediated by T cells
These results suggest that Human cytomegalovirus (HCMV) infection may differently influence the B cell compartment distribution in multiple sclerosis (MS) depending on the clinical form
A representative case is illustrated in the figure, showing proportions of B cell subsets therapy in HCMV(−) relapsing-remitting MS (RRMS) was associated with increased NB and reduced SMB cells, resembling the effect of HCMV infection on these B cell subsets described above, which dampened the differences with HCMV(+) treated cases (Fig. 3b). These results revealed that HCMV infection may influence the distribution of B cell subsets in MS patients modulating the effects of IFNβ
Summary
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system classically considered to be mediated by T cells. HCMV chronic infection leads to marked changes in the immune system [7], mainly characterized by the differentiation and expansion of specific T cells [8] and adaptive NK cell subsets expressing the CD94/NKG2C activating receptor [9], a phenotypic feature that has been associated with reduced MS progression [10]. In. Zabalza et al Journal of Neuroinflammation (2020) 17:161 this study, we evaluated whether HCMV may have an influence on the B cell compartment in MS patients according to clinical features of the disease. Human cytomegalovirus (HCMV) infection has been recently associated with a low risk of multiple sclerosis (MS), yet the basis behind this observation remains uncertain. We aimed to determine in MS patients whether HCMV induces modifications in the peripheral B cell compartment
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