The Immunologic Profile Is “Permanently” Changed in Patients with Pemphigus and a Complete Response to Rituximab

Long-term remission of pemphigus after rituximab treatment is associated with loss of desmoglein B cell response.

Pemphigus is a chronic autoimmune blistering disorder mediated by autoantibodies against desmogleins 1 and 3. Disruption of desmosomes causes acantholysis, resulting in skin and mucosal blisters. The mainstay of treatment is immunosuppression, often with prednisone. Many open-label trials and small case series have demonstrated the short-term effectiveness of the anti-CD20 antibody, rituximab. Several clinicians have reported long-term remissions in some patients, but the mechanism of this response has not been fully worked out. These authors evaluated the clinical course, after a median 79-month follow-up period, of 22 patients from various European centers who received rituximab treatment for pemphigus; most of these patients had taken part in a landmark rituximab study (N Engl J Med 2007; 357:545).

B-cell depletion occurs after rituximab therapy. At about 6 months, B-cell reconstitution occurs. These researchers compared the immunologic profiles of B cells and T cells at baseline and at 6 years in 13 complete rituximab responders and 9 incomplete responders.

As the B cells returned, different profiles were evident in the two groups. Specifically, B cells that secrete interleukin-10 were found in the responders as well as an absence of desmoglein-specific circulating IgG⁺ B lymphocytes. Desmoglein-specific circulating IgG⁺ B lymphocytes remained in the patients with incomplete responses, as did B cells specific for infectious agents. The latter finding may explain why severe infections were absent in these patients.

Comment

This important observation suggests that reconstitution of B cells following rituximab therapy might not include pathogenic regulatory B cells and could result in a potential depletion of T lymphocytes that interact with these B cells. Perhaps rituximab treatment should be undertaken earlier in a patient's course, so that the immune reconstitution might more reliably occur. Whether rituximab will become a first-line therapy for pemphigus remains to be seen.

Reviewing Authors

Jeffrey P. Callen, MD

Disclosures

Consultant / Advisory board XOMA; Eli Lilly; Celgene

Equity Various trust accounts

Editorial boards JAMA Dermatology; UpToDate

Leadership positions in professional societies Association of Professors of Dermatology (President-Elect)

Jeffrey P. Callen, MD

Disclosures

Consultant / Advisory board XOMA; Eli Lilly; Celgene

Equity Various trust accounts

Editorial boards JAMA Dermatology; UpToDate

Leadership positions in professional societies Association of Professors of Dermatology (President-Elect)

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Kenneth Y. Tsai, MD, PhD

Disclosures

Grant / Research support American Association for Cancer Research – Landon Foundation; National Institutes of Health/National Cancer Institute; Cancer Prevention Research Institute of Texas

Editorial BoardsJournal of the American Academy of Dermatology

Citation(s):

Colliou N et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med 2013 Mar 6; 5:175ra30. (http://dx.doi.org/10.1126/scitranslmed.3005166)