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- Title
Th1 - CD11c<sup>+</sup> B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis.
- Authors
Kimura, Kimitoshi; Lin, Youwei; Yamaguchi, Hiromi; Sato, Wakiro; Takewaki, Daiki; Minote, Misako; Doi, Yoshimitsu; Okamoto, Tomoko; Takahashi, Ryosuke; Kondo, Takayuki; Yamamura, Takashi
- Abstract
<bold>Objective: </bold>Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response.<bold>Methods: </bold>We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response.<bold>Results: </bold>The frequency of IFN-γ+ Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation-related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c+ B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c+ B cells would increase in response to exogenous IFN-γ compared to IL-4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c+ B cells takes place in patients with multiple sclerosis. Interestingly, CD11c+ B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.<bold>Interpretation: </bold>Taken together, we postulate that Th1 cell - CD11c+ B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595-611.
- Subjects
B cells; B cell receptors; AUTOIMMUNE diseases; PLASMAPHERESIS; TH1 cells; MULTIPLE sclerosis
- Publication
Annals of Neurology, 2021, Vol 90, Issue 4, p595
- ISSN
0364-5134
- Publication type
journal article
- DOI
10.1002/ana.26202