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B-Cell Reconstitution and BAFF After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis

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Abstract

Introduction

Treatment with alemtuzumab is highly effective in relapsing–remitting multiple sclerosis; however, 30% of patients develop autoimmunity. Alemtuzumab (previously called Campath 1-H) induces a prolonged T-cell lymphopenia with memory cells dominating the reconstituting T-cell pool for at least 3 months.

Results

Here we show that B-cell recovery is rapid, returning to baseline by 3 months and rising to 165% of baseline by 12 months after treatment. Immature transitional 1 B cells are the predominant cell type 1 month after treatment. This coincides with a surge in serum B-cell activating factor (BAFF), which remains elevated by 33% for at least 12 months after alemtuzumab. BAFF is critical for transition to the mature naive B-cell phenotype, which dominates from 3 months after alemtuzumab. Differentiation to memory B cells is slow so there are radical and prolonged alterations to the B-cell pool after alemtuzumab.

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Acknowledgments

Patients in this study were part of two clinical trials funded in part by Genzyme and conducted at the Addenbrooke's Wellcome Trust Clinical Research Facility. AC is funded in part by the NIHR Biomedical Research Centre, and ST is funded by UCB-Celltech.

Dr. A Coles and Dr. J Jones received honoraria and travel expenses from Genzyme to attend advisory board meetings, and our department has received research funding from Genzyme.

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Correspondence to Sara A. J. Thompson.

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Thompson, S.A.J., Jones, J.L., Cox, A.L. et al. B-Cell Reconstitution and BAFF After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis. J Clin Immunol 30, 99–105 (2010). https://doi.org/10.1007/s10875-009-9327-3

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  • DOI: https://doi.org/10.1007/s10875-009-9327-3

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