title: Dichotomy of autoreactive Th1 and Th2 cell responses to desmoglein 3 in patients with pemphigus vulgaris (PV) and healthy carriers of PV-associated HLA class II alleles.
abstract: Pemphigus vulgaris (PV) is the most severe autoimmune bullous skin disorder and is primarily associated with circulating autoantibodies (autoAb) against desmoglein 3 (Dsg3). In light of recent evidence that autoreactive T cells are critical for the induction and regulation of Ab production, the goal of this study was to characterize and quantitate autoreactive T cells in patients with PV and healthy controls. Peripheral Dsg3-reactive Th cells from 28 patients with acute-onset, chronic active, and remittent PV were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all studied PV patients, while the number of autoreactive Th1 cells exceeded those of Th2 cells in chronic active PV. In contrast, healthy carriers of the PV-associated HLA class II alleles, DRB1*0402 and DQB1*0503, exhibited exclusively Dsg3-reactive Th1 cell responses, while healthy carriers of other HLA class II alleles did not. Moreover, the presence of IgG1 and IgG4 against Dsg3 was directly related to the ratio of Dsg3-reactive Th1/Th2 cells. T cell recognition of Dsg3 was restricted by HLA-DRB1*0402 and DQB1*0503 in PV patients and Dsg3-responsive healthy donors. These observations strongly suggest 1) that the appearance of Dsg3-reactive Th2 cells is restricted to patients with PV; 2) that specific HLA class II alleles that are prevalent in PV are critical for T cell recognition of Dsg3 in PV patients and Dsg3-responsive healthy donors; and 3) that autoAb production is associated with both Th1 and Th2 cells.
authors.affiliation: Departments of Dermatology, University of Erlangen-Nurnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Veldman
authors.forename: Angelika
authors.initials: A
authors.lastname: Stauber
authors.forename: Ralf
authors.initials: R
authors.lastname: Wassmuth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Uter
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
mesh_terms: D000208:Acute Disease; D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D015820:Cadherins / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D002908:Chronic Disease; D002999:Clone Cells; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D051184:Desmoglein 3; D006580:Genetic Carrier Screening; D006680:HLA Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D018189:Immunomagnetic Separation; D018655:Lymphocyte Count; D010392:Pemphigus / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D015820:Cadherins; D016207:Cytokines; C071894:DSG3 protein, human; D051184:Desmoglein 3; D006680:HLA Antigens; D006681:HLA-D Antigens