Abstract
ObjectivesAt the end of a 60‐day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B‐cell subsets. This study investigated phototherapy‐associated changes to cytokine responses of B cells when exposed to a TLR7 ligand.MethodsPBMCs from participants of the PhoCIS (Phototherapy for Clinically Isolated Syndrome) trial taken before (day 1) and after phototherapy for 8 weeks (day 60) were incubated with, or without, the TLR7 ligand, R848, for 18 h. Production of TNF and IL‐10 in seven B‐cell subsets was examined, with cytokine responses in each individual at day 60, adjusted for responses at day 1. Paired PBMCs were from participants administered phototherapy (n = 7) or controls (n = 6).ResultsAt day 60, significantly fewer B cells, particularly marginal zone‐like B cells (CD27+/IgD+), from participants administered phototherapy produced TNF in response to TLR7 stimulation. When responses by seven B‐cell subsets were analysed together using multivariate methods, a phototherapy‐specific signature was observed. An increased responsiveness from day 1 to day 60 in IgM‐only memory B cells (CD27+/IgD−/IgM+) after TLR7 stimulation also predicted slower progression from CIS to MS. Phototherapy was without significant effect on B‐cell IL‐10 production.ConclusionsReduced TNF responses after TLR7 stimulation in marginal zone‐like B cells from participants administered phototherapy suggested treatment‐associated priming effects that were detected upon subsequent polyclonal B‐cell activation. Changes in responsiveness to TLR7 stimulation also suggested that IgM‐only memory B cells may be important in conversion from CIS to MS.
Highlights
Genetic predisposition to multiple sclerosis (MS) explains only a fraction of the disease risk.[1]
In our original study analysing bloods from the complete PhoCIS cohort, narrowband UVB phototherapy increased the proportion of naive B cells and decreased the proportion of MBC (CD27+/IgDÀ) within the B-cell population.[14]
B-cell subsets were identified in the CD19+/CD20+ population as per Figure 1a and included IgM+ and IgMÀ double-negative (DN), naive and marginal zone (MZ)-like B cells, IgM-only MBC and switched MBC (Sw MBC)
Summary
Genetic predisposition to multiple sclerosis (MS) explains only a fraction of the disease risk.[1]. The independence of reduced sun exposure and low 25(OH)D as risk factors for MS suggests that there may be several potentially beneficial effects, other than vitamin D production in UV-irradiated skin.[7,8] there have been disappointing results following several trials of vitamin D supplementation to patients with MS, who did not gain the hoped-for benefit suggested by the inverse associations reported for MS incidence and 25(OH)D levels, as reviewed.[9,10]
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