title: Extremities of the N-terminus of envoplakin and C-terminus of its linker subdomain are major epitopes of paraneoplastic pemphigus.
abstract: BACKGROUND
  Autoantibodies against N-terminal domains and linker subdomains of envoplakin (EVPL) and periplakin (PPL) were frequently detected in sera of paraneoplastic pemphigus(PNP) patients.
  
  
  OBJECTIVE
  To further investigate finer epitopes of EVPL and PPL, and evaluate their associations with clinical aspects of PNP.
  
  
  METHODS
  We produced 12 overlapping truncated fragments of these regions in Escherichia coli, and measured their reactivities to sera of 65 PNP patients and 50 healthy volunteers by enzyme-linked immunosorbent assays (ELISA). Then appropriate statistics were performed to evaluate the correlation between antibodies against different fragments and clinical information of patients.
  
  
  RESULTS
  EVPL-N1 (aa1-141) and EVPL-L3 (aa1684-1784) were recognized by PNP sera at the same sensitivity of 75.38% (49/65) with specificities of 98% and 92%, respectively. Although neoplasm types were not associated with any fragment, the ELISA of these fragments and indirect immunofluorescence on rat bladder complemented each other in detecting PNP. Meanwhile, levels of autoantibodies against EVPL-N3 were elevated with PNP accompanied with bronchiolitis obliterans or presented with lichen planus-like lesions (P<0.05). No influence of autoantibodies against any fragments on prognosis of the patients was observed by Cox regression test, though antibodies against some fragments were higher in the dead patients.
  
  
  CONCLUSIONS
  The study proved antigenic epitopes were mainly concentrated on EVPL-N1 and EVPL-L3 in PNP. Autoantibodies against EVPL-N3 might associate with those patients accompanied with bronchiolitis obliterans or presented with lichen planus-like lesions.
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: xuewang@bjmu.edu.cn.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: pumpchange1989@163.com.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: gongchengyx@sohu.com.
authors.forename: Junyu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: doctoryangpeng@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: xixue_chen@163.com.
authors.forename: Xixue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: tup0207@sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Tu
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: bjzhuxj@163.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: zhi_liu@med.unc.edu.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing 100034, China; Beijing Key Laboratory of Molecular Diagnosis of Dermatoses, Beijing 100034, China. Electronic address: wangmy@pku.edu.cn.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D019540:Area Under Curve; D001323:Autoantibodies / Q000737:chemistry; D001989:Bronchiolitis Obliterans / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008010:Lichen Planus / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*; D051179:Plakins / Q000737:chemistry / Q000276:immunology; D016016:Proportional Hazards Models; D000072417:Protein Domains; D011498:Protein Precursors / Q000737:chemistry* / Q000276:immunology; D012372:ROC Curve; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D012680:Sensitivity and Specificity; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D008565:Membrane Proteins; C491674:PPL protein, human; D051179:Plakins; D011498:Protein Precursors; D011994:Recombinant Proteins; C100754:envoplakin
keywords: Envoplakin; Epitope; Paraneoplastic pemphigus; Periplakin