1. ¹Department of Dermatology and Allergology, Philipps University, Marburg, Germany
2. ²Department of Dermatology, Klinikum Nord, Nürnberg, Germany

Correspondence: Dr Rüdiger Eming, Department of Dermatology and Allergology, Philipps University Marburg, Deutschhausstrasse 9, Marburg D35037, Germany. E-mail: eming@med.uni-marburg.de

³These authors contributed equally to this work.

Received 4 December 2007; Revised 2 April 2008; Accepted 5 May 2008; Published online 19 June 2008.

Abstract

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease affecting the skin and mucous membranes. Autoreactive CD4⁺ T helper (Th) lymphocytes are crucial for the autoantibody response against the desmosomal adhesion molecules, desmoglein (dsg)-3 and dsg1. Eleven patients with extensive PV were treated with the anti-CD20 antibody, rituximab (375 mg per m² body surface area once weekly for 4 weeks). Frequencies of autoreactive CD4⁺ Th cells in the peripheral blood of the PV patients were determined 0, 1, 3, 6, and 12 months after rituximab treatment. Additionally, the clinical response was evaluated and serum autoantibody titers were quantified by ELISA. Rituximab induced peripheral B-cell depletion for 6–12 months, leading to a dramatic decline of serum autoantibodies and significant clinical improvement in all PV patients. The frequencies of dsg3-specific CD4⁺ Th1 and Th2 cells decreased significantly for 6 and 12 months, respectively, while the overall count of CD3⁺CD4⁺ T lymphocytes and the frequency of tetanus toxoid-reactive CD4⁺ Th cells remained unaffected. Our findings indicate that the response to rituximab in PV involves two mechanisms: (1) the depletion of autoreactive B cells and (2) the herein demonstrated, presumably specific downregulation of dsg3-specific CD4⁺ Th cells.