title: The protease inhibitor alpha-2-macroglobulin-like-1 is the p170 antigen recognized by paraneoplastic pemphigus autoantibodies in human.
abstract: BACKGROUND
  Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown.
  
  
  RESULTS
  Using an immunoprecipitation and mass spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera recognize alpha-2-macroglobuline-like-1 (A2ML1), while none of the control sera obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus and normal subjects does.
  
  
  CONCLUSIONS
  Our study unravels a broad range protease inhibitor as a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome and opens a new challenging investigation avenue for a better understanding of PNP pathogenesis.
authors.affiliation: Department of Dermatology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. isabelle.schepens@insel.ch
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schepens
authors.forename: Fabienne
authors.initials: F
authors.lastname: Jaunin
authors.forename: Nadja
authors.initials: N
authors.lastname: Begre
authors.forename: Ursula
authors.initials: U
authors.lastname: Läderach
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Bertrand
authors.initials: B
authors.lastname: Favre
authors.forename: Luca
authors.initials: L
authors.lastname: Borradori
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D003470:Culture Media; D004817:Epidermis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000166:cytology; D011480:Protease Inhibitors / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019163:Reducing Agents / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D000511:alpha-Macroglobulins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: C510358:A2ML1 protein, human; D001323:Autoantibodies; D001324:Autoantigens; D003470:Culture Media; D011480:Protease Inhibitors; D019163:Reducing Agents; D000511:alpha-Macroglobulins
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