Rituximab exerts a dual effect in pemphigus vulgaris.
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 m(2) 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.
Department of Dermatology and Allergology, Philipps University, Marburg, Germany. eming@med.uni-marburg.de
Rüdiger
R
Eming
Angela
A
Nagel
Sonja
S
Wolff-Franke
Eva
E
Podstawa
Dirk
D
Debus
Michael
M
Hertl
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D051184:Desmoglein 3 / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab; D013745:Tetanus Toxoid / Q000737:chemistry; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D017252:CD3 Complex; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007155:Immunologic Factors; D013745:Tetanus Toxoid; D000069283:Rituximab