title: Serological proteome analysis reveals new specific biases in the IgM and IgG autoantibody repertoires in autoimmune polyendocrine syndrome type 1.
abstract: OBJECTIVE
  Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown, which results in tissue-specific autoimmune diseases.
  
  
  METHODS
  To evaluate the effect of a well-defined T-cell repertoire impairment on humoral self-reactive fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed using both one- and two-dimensional western blotting approaches against a broad spectrum of peripheral tissue antigens.
  
  
  METHODS
  Autoantibody patterns of APS 1 patients were compared with those of subjects affected by other autoimmune endocrinopathies (OAE) and healthy controls.
  
  
  RESULTS
  Using a Chi-square test, significant changes in the Ab repertoire were found when intergroup patterns were compared. A singular distortion of both serum self-IgG and self-IgM repertoires was noted in APS 1 patients. The molecular characterization of these antigenic targets was conducted using a proteomic approach. In this context, autoantibodies recognized more significantly either tissue-specific antigens, such as pancreatic amylase, pancreatic triacylglycerol lipase and pancreatic regenerating protein 1α, or widely distributed antigens, such as peroxiredoxin-2, heat shock cognate 71-kDa protein and aldose reductase. As expected, a well-defined self-reactive T-cell repertoire impairment, as described in APS 1 patients, affected the tissue-specific self-IgG repertoire. Interestingly, discriminant IgM reactivities targeting both tissue-specific and more widely expressed antigens were also specifically observed in APS 1 patients. Using recombinant targets, we observed that post translational modifications of these specific antigens impacted upon their recognition.
  
  
  CONCLUSIONS
  The data suggest that T-cell-dependent but also T-cell-independent mechanisms are involved in the dynamic evolution of autoimmunity in APS 1.
authors: a CHRU Lille, Institut d'Immunologie - Centre de Biologie Pathologie et Génétique , Lille , France .|b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .
authors: Sylvain
authors: S
authors: Dubucquoi
authors: b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .|d CHRU Lille Service d'Endocrinologie , Lille , France .
authors: Emmanuelle
authors: E
authors: Proust-Lemoine
authors: e Department of Human Metabolism , University of Sheffield , Sheffield , UK .
authors: E Helen
authors: EH
authors: Kemp
authors: b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .|d CHRU Lille Service d'Endocrinologie , Lille , France .
authors: Amélie
authors: A
authors: Ryndak
authors: a CHRU Lille, Institut d'Immunologie - Centre de Biologie Pathologie et Génétique , Lille , France .|b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .
authors: Virginie
authors: V
authors: Lefèvre-Dutoit
authors: a CHRU Lille, Institut d'Immunologie - Centre de Biologie Pathologie et Génétique , Lille , France .|b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .
authors: Marine
authors: M
authors: Bellart
authors: f Laboratoire de génétique moléculaire , Rouen , France , and.
authors: Pascale
authors: P
authors: Saugier-Véber
authors: c Univ Lille Nord de France , Lille , France .|g UArtois, LBHE , EA 2465 , Lens , France.
authors: Sophie
authors: S
authors: Duban-Deweer
authors: b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .|d CHRU Lille Service d'Endocrinologie , Lille , France .
authors: Jean-Louis
authors: JL
authors: Wémeau
authors: a CHRU Lille, Institut d'Immunologie - Centre de Biologie Pathologie et Génétique , Lille , France .|b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .
authors: Lionel
authors: L
authors: Prin
authors: b UDSL, EA 2686, UFR Médecine , Lille , France .|c Univ Lille Nord de France , Lille , France .
authors: Didier
authors: D
authors: Lefranc
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics / Q000276:immunology; D000681:Amylases / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D001324:Autoantigens / Q000097:blood / Q000737:chemistry* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015870:Gene Expression; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D007075:Immunoglobulin M / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D008049:Lipase / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D054464:Peroxiredoxins / Q000235:genetics / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology; D020543:Proteome / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D000449:Aldehyde Reductase; D000681:Amylases; D001323:Autoantibodies; D001324:Autoantigens; D050883:HSC70 Heat-Shock Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008049:Lipase; D054464:Peroxiredoxins; D020543:Proteome; D014157:Transcription Factors; D000096927:AIRE Protein; C494371:HSPA8 protein, human; C086065:PRDX2 protein, human
keywords: AIRE; APS 1; T-dependent and T-independent mechanisms; autoantibody repertoire; post translational modifications