B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis.
BACKGROUND
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.
Thompson
Sara A J
SA
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. st293@medschl.cam.ac.uk
Jones
Joanne L
JL
Cox
Amanda L
AL
Compston
D Alastair S
DA
Coles
Alasdair J
AJ
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D000074323:Alemtuzumab