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Open Access 01-12-2011 | Research

Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

Authors: Klaus Lehmann-Horn, Eva Schleich, Deetje Hertzenberg, Alexander Hapfelmeier, Tania Kümpfel, Nikolas von Bubnoff, Reinhard Hohlfeld, Achim Berthele, Bernhard Hemmer, Martin S Weber

Published in: Journal of Neuroinflammation | Issue 1/2011

Abstract

Background

Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders.

Methods

Myelin oligodendrocyte glycoprotein (MOG) peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg) and cytokine production of CD11b⁺ antigen presenting cells (APC) were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM).

Results

We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b⁺ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM.

Conclusions

These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and effectiveness may further advance by selectively targeting pathogenic B-cell function.

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Title: Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders
Authors: Klaus Lehmann-Horn
Eva Schleich
Deetje Hertzenberg
Alexander Hapfelmeier
Tania Kümpfel
Nikolas von Bubnoff
Reinhard Hohlfeld
Achim Berthele
Bernhard Hemmer
Martin S Weber
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-8-146

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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