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B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis.


ABSTRACT:

Objective

To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).

Methods

In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.

Results

Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.

Conclusions

We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.

SUBMITTER: Schwarz A 

PROVIDER: S-EPMC5182056 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis.

Schwarz Alexander A   Balint Bettina B   Korporal-Kuhnke Mirjam M   Jarius Sven S   von Engelhardt Kathrin K   Fürwentsches Alexandra A   Bussmann Cornelia C   Ebinger Friedrich F   Wildemann Brigitte B   Haas Jürgen J  

Neurology(R) neuroimmunology & neuroinflammation 20161215 1


<h4>Objective</h4>To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).<h4>Methods</h4>In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, n  ...[more]

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