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

Journal of Neuroinflammation

Martin S Weber¹  Bernhard Hemmer¹  Achim Berthele¹  Reinhard Hohlfeld⁴  Nikolas von Bubnoff³  Tania Kümpfel⁴  Alexander Hapfelmeier²  Deetje Hertzenberg¹  Eva Schleich¹  Klaus Lehmann-Horn¹ 

[1] Department of Neurology, Technische Universität München, Munich, Germany;Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany;Department of Internal Medicine, Technische Universität München, Munich, Germany;Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Munich, Germany

关键词: experimental autoimmune encephalomyelitis;    monocytes;    B-cell regulation;    anti-CD20;    neuromyelitis optica;    multiple sclerosis;   

Others  :  1213042
DOI  :  10.1186/1742-2094-8-146

 received in 2011-08-24, accepted in 2011-10-26,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Lehmann-Horn et al; licensee BioMed Central Ltd.

【 图 表 】

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