title: Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize epitopes clustered in distinct regions of BP180 and BP230.
abstract: Bullous pemphigoid (BP) is a well-characterized model of autoantibody-mediated autoimmunity, which presumably depends on autoreactive Th cells that promote the activation of autoreactive B cells. The two major autoantigens of BP are BP180 and BP230, two components of dermoepidermal adhesion complexes. Both, autoreactive Th cell responses and autoantibody profiles were characterized in 35 patients with acute onset BP using BP180 and BP230 proteins. Our findings indicate the following: 1) autoreactive Th cells recognized epitopes within the NH2-terminal (77.1%), COOH-terminal (65.7%), and central portion (57.1%) of the BP180 ectodomain; 2) IgG autoantibodies were found to exhibit similar or identical reactivity against the NH2-terminal (82.8%), COOH-terminal (77.1%), and central portion (37.1%) of the BP180 ectodomain; 3) T and B cell reactivity with the NH2-terminal portion of the BP180 ectodomain was associated with extensive BP, whereas the central portion was more frequently recognized in limited BP; 4) only 7 of 16 (43.7%) and 6 of 16 (37.5%) BP patients showed a Th cellular response against the COOH- and NH2-terminal regions of BP230, respectively, whereas 5) IgG reactivity against the COOH- and NH2-termini of BP230 was detected in 5 of 16 (31.3%) and 6 of 16 (37.5%) patients, respectively. These results demonstrate that Th and B cell reactivities against BP180, are, in contrast to BP230 reactivity, almost constantly detectable in BP patients, and differential epitope recognition of BP180 seems to be associated with distinct clinical severity. These observations support the concept that BP180, but not BP230, is the primary autoantigen of BP critical for disease development.
authors.affiliation: Department of Dermatology, Friedrich-Alexander-University, Erlangen, Germany.
authors.forename: Sybille
authors.initials: S
authors.lastname: Thoma-Uszynski
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Uter
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwietzke
authors.forename: Gerold
authors.initials: G
authors.lastname: Schuler
authors.forename: Luca
authors.initials: L
authors.lastname: Borradori
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism*; D000071821:Dystonin; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human