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

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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.


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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  1. Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359:1786–01.

    Article  PubMed  Google Scholar 

  2. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502–17.

    Article  PubMed  CAS  Google Scholar 

  3. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med. 2008;358:676–88.

    Article  PubMed  CAS  Google Scholar 

  4. Meinl E, Krumbholz M, Hohlfeld R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann Neurol. 2006;59:880–92.

    Article  PubMed  CAS  Google Scholar 

  5. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 2004;14:164–74.

    Article  PubMed  Google Scholar 

  6. Serafini B, Rosicarelli B, Franciotta D, Magliozzi R, Reynolds R, Cinque P, et al. Dysregulated Epstein–Barr virus infection in the multiple sclerosis brain. J Exp Med. 2007;204:2899–912.

    Article  PubMed  CAS  Google Scholar 

  7. Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood. 1993;82:807–12.

    PubMed  CAS  Google Scholar 

  8. Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005;35:3332–42.

    Article  PubMed  CAS  Google Scholar 

  9. Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253:98–108.

    Article  PubMed  Google Scholar 

  10. Agematsu K, Hokibara S, Nagumo H, Komiyama A. CD27: a memory B-cell marker. Immunol Today. 2000;21:204–6.

    Article  PubMed  CAS  Google Scholar 

  11. Carsetti R, Kohler G, Lamers MC. Transitional B cells are the target of negative selection in the B cell compartment. J Exp Med. 1995;181:2129–40.

    Article  PubMed  CAS  Google Scholar 

  12. Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, et al. BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med. 2000;192:1453–66.

    Article  PubMed  CAS  Google Scholar 

  13. Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001;293:2111–4.

    Article  PubMed  CAS  Google Scholar 

  14. Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404:995–9.

    Article  PubMed  CAS  Google Scholar 

  15. Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, Bhan AK, et al. Impaired IgA class switching in APRIL-deficient mice. Proc Natl Acad Sci USA. 2004;101:3903–8.

    Article  PubMed  CAS  Google Scholar 

  16. He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity. 2007;26:812–26.

    Article  PubMed  CAS  Google Scholar 

  17. Sakurai D, Hase H, Kanno Y, Kojima H, Okumura K, Kobata T. TACI regulates IgA production by APRIL in collaboration with HSPG. Blood. 2007;109:2961–7.

    PubMed  CAS  Google Scholar 

  18. Huard B, McKee T, Bosshard C, Durual S, Matthes T, Myit S, et al. APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa. J Clin Invest. 2008;118:2887–95.

    PubMed  CAS  Google Scholar 

  19. Anolik JH, Barnard J, Owen T, Zheng B, Kemshetti S, Looney RJ, et al. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum. 2007;56:3044–56.

    Article  PubMed  CAS  Google Scholar 

  20. Roll P, Palanichamy A, Kneitz C, Dorner T, Tony HP. Regeneration of B cell subsets after transient B cell depletion using anti-CD20 antibodies in rheumatoid arthritis. Arthritis Rheum. 2006;54:2377–86.

    Article  PubMed  CAS  Google Scholar 

  21. Roll P, Dorner T, Tony HP. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566–75.

    Article  PubMed  CAS  Google Scholar 

  22. Avanzini MA, Locatelli F, Dos SC, Maccario R, Lenta E, Oliveri M, et al. B lymphocyte reconstitution after hematopoietic stem cell transplantation: functional immaturity and slow recovery of memory CD27+ B cells. Exp Hematol. 2005;33:480–6.

    Article  PubMed  CAS  Google Scholar 

  23. Hoek KL, Antony P, Lowe J, Shinners N, Sarmah B, Wente SR, et al. Transitional B cell fate is associated with developmental stage-specific regulation of diacylglycerol and calcium signaling upon B cell receptor engagement. J Immunol. 2006;177:5405–13.

    PubMed  CAS  Google Scholar 

  24. Coles AJ, Wing M, Smith S, Coraddu F, Greer S, Taylor C, et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet. 1999;354:1691–5.

    Article  PubMed  CAS  Google Scholar 

  25. Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697–710.

    Article  PubMed  CAS  Google Scholar 

  26. Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Xu D, et al. B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003;48:3475–86.

    Article  PubMed  Google Scholar 

  27. Zhou Z, Chen Z, Li H, Chen X, Xu J, Gu D, et al. BAFF and BAFF-R of peripheral blood and spleen mononuclear cells in idiopathic thrombocytopenic purpura. Autoimmunity. 2009;42:112–9.

    Article  PubMed  CAS  Google Scholar 

  28. Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, et al. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome. J Clin Invest. 2002;109:59–68.

    PubMed  CAS  Google Scholar 

  29. Krumbholz M, Specks U, Wick M, Kalled SL, Jenne D, Meinl E. BAFF is elevated in serum of patients with Wegener's granulomatosis. J Autoimmun. 2005;25:298–302.

    Article  PubMed  CAS  Google Scholar 

  30. Daridon C, Pers JO, Devauchelle V, Martins-Carvalho C, Hutin P, Pennec YL, et al. Identification of transitional type II B cells in the salivary glands of patients with Sjogren's syndrome. Arthritis Rheum. 2006;54:2280–8.

    Article  PubMed  CAS  Google Scholar 

  31. Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F, et al. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004;20:785–98.

    Article  PubMed  CAS  Google Scholar 

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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).

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