Editors' ChoiceAutoimmunity

A Tinier Target for B Cell Therapy in Multiple Sclerosis

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Science Translational Medicine  16 May 2012:
Vol. 4, Issue 134, pp. 134ec84
DOI: 10.1126/scitranslmed.3004284

Multiple sclerosis (MS) is a progressive autoimmune disease that attacks the nervous system. Recent work indicates that B cells play a critical role in this disorder, and B cell depletion can help patients with MS. It is critical to know how B cells participate in MS because the long-term safety of repeated B cell depletion remains uncertain. Barr et al., working with a mouse model of MS and patient samples, narrow our focus to B cells that produce the cytokine interleukin-6 (IL-6). With anti–IL-6 agents now available, more focused treatment for MS patients may be possible.

A human antibody to CD20 (anti-CD20) that depletes B cells improves outcomes for MS patients. In a mouse MS model, Barr et al. show that B cell depletion only ameliorates symptoms of MS when the B cells express IL-6. They then extend their findings to show that MS patients have elevated IL-6 expression in B cells and that treatment with anti-CD20 unexpectedly eliminates the excess B cell IL-6.

The authors rightly caution that it cannot be assumed that anti-CD20 therapy is selectively depleting pathogenic B cells that produce IL-6 in human MS patients. Nevertheless, optimism is warranted because in other models of autoimmune disease, specific B cell populations are differentially sensitive to anti-CD20 agents. Therapy against IL-6, which is relatively safe long-term in rheumatoid arthritis patients, may provide a new, more focused option for treatment of patients with MS.

T. A. Barr et al., B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells. J. Exp. Med. 30 April 2012 (10.1084/jem.20111675). [Abstract]

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