Research ArticleAutoimmunity

Long-Term Remissions of Severe Pemphigus After Rituximab Therapy Are Associated with Prolonged Failure of Desmoglein B Cell Response

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Science Translational Medicine  06 Mar 2013:
Vol. 5, Issue 175, pp. 175ra30
DOI: 10.1126/scitranslmed.3005166

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A Blistering Attack on Autoimmunity

The devastating effects of autoimmune diseases like type 1 diabetes and multiple sclerosis are front-page news. However, rare autoimmune diseases may be even more distressing in their relative anonymity. One such condition is pemphigus, which is a severe blistering condition caused by autoantibodies to adhesion proteins in the skin and mucus. The B cell–depleting antibody rituximab has been shown to treat pemphigus short term in early clinical trials. Now, Colliou et al. find that rituximab therapy can help pemphigus patients even after 6 years, in part by reshaping the B cell repertoire during reconstitution.

The authors followed pemphigus patients from their early trial out at least 6 years after rituximab therapy. They found that nearly two-thirds of patients achieved a long-term complete response—either completely off of therapy or when treated with low levels of supplementary prednisone. They then compared patients with complete response to those with incomplete response to look at differences in reconstitution of the B cell compartment. Patients with complete response had a greater proportion of naïve and transitional B cells than those with incomplete response, which suggests a barrier to B cell maturation. Indeed, many of these transitional B cells secreted the regulatory cytokine interleukin-10. Moreover, complete responders had a specific loss of anti–desmoglein-specific B cells, which are pathogenic in pemphigus patients, but not B cells that respond to infectious agents. Together, these data suggest that B cell repertoire is reshaped after rituximab therapy, allowing for long-term effects in addition to the short-term loss of pathogenic B cells. If these observations are confirmed in large studies, these data could form the basis for a new frontline therapy for recalcitrant pemphigus.

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