Targeted Immunotherapy with Rituximab Leads to a Transient Alteration of the IgG Autoantibody Profile in Pemphigus Vulgaris. (26th April 2010)

• Record Type: Journal Article
• Authors: Müller, Ralf; Hunzelmann, Nicolas; Baur, Vera; Siebenhaar, Guido; Wenzel, Elke; Eming, Rüdiger; Niedermeier, Andrea; Musette, Philippe; Joly, Pascal; Hertl, Michael
• Other Names: Koch Peter J. Academic Editor.
• Is Part Of: Dermatology research and practice. Volume 2010(2010)
• Publication Date: 2010-04-26
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; Skin -- Diseases -- Treatment -- Periodicals; 616.5005
• DOI: 10.1155/2010/321950
• Languages: English
• ISSNs: 1687-6105

Abstract

Abstract : In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of keratinocyteadhesion. The aim of the present study was to study the effect of the B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients who were followed up clinically and serologically by Dsg3 ELISA over 12-24 months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3 (Dsc3EC1-5). Specifically, 14/22 showed IgG reactivity against the Dsg3EC1 subdomain, 5/22 patients against Dsg3EC2, 7/22 against Dsg3EC3, 11/22 against Dsg3EC4, and 2/22 against Dsg3EC5. Within 6 months after rituximab, all the patients showed significant clinical improvement and reduced IgG against Dsg3 (5/22) and the various subdomains, that is, Dsg3EC1 (7/22), Dsg3EC2 (3/22), Dsg3EC3 (2/22), sg3EC4 (2/22), and Dsg3EC5 (0/22). During the entire observation period, 6/22 PV patients experienced a clinical relapse which was associated with the reappearance of IgG against previously recognized Dsg3 subdomains, particularly against the Dsg3EC1. Thus, in PV, rituximab only temporarily depletes pathogenic B cell responses against distinct subdomains of Dsg3 which reappear upon clinical relapse.