title: Crohn's disease-specific pancreatic autoantibodies are specifically present in ruminants with paratuberculosis: implications for the pathogenesis of the human disease.
abstract: Mycobacterium avium subspecies paratuberculosis (MAP) induces paratuberculosis (ptb) in ruminants and has clinical and histological features resebling Crohn's disease (CD). Pancreatic autoantibodies (PAB) targeting glycoprotein 2 (GP2) are specifically found in CD, but it is currently unknown whether these autoantibodies can be found in ruminants with ptb. IgG anti-MAP and anti-GP2 antibodies were tested by ELISA in 286 ruminants (212 sheep and 74 cattle). PAB testing was performed by indirect immunofluorescence (IIF) using anti-sheep or anti-cattle specific antisera. PCR analysis confirmed the presence of MAP in anti-MAP positive samples. Anti-GP2 antibodies were more prevalent in anti-MAP antibody positive (26.9%) than in anti-MAP negative ruminants (8.7%, p < 0.001). Anti-GP2 antibodies were found in 16/70 (22.9%) anti-MAP positive sheep compared to 10/142 (7%, p = 0.001) anti-MAP antibody negative and in anti-MAP positive cattle than in negative counterparts (5/8 versus 8/66, p = 0.003). Absorbance values for anti-GP2 antibodies were higher in cattle than in sheep (mean 21 AU/mL ± 25.4SD versus 12.2 AU/mL ± 23 SD, p < 0.001). There was no correlation between anti-GP2 and anti-MAP antibody concentrations. Anti-GP2 antibodies persisted up to 1/1000 and showed the characteristic IIF pancreatic pattern seen by anti-GP2 antibody positive CD samples. This is the first study to demonstrate the presence of CD-specific GP2-reactive pancreatic autoantibodies in MAP-infected ruminants. Our data suggest that CD and ptb are characterised by an antigen-driven loss of immunological tolerance to GP2, implying commonalities in the immunopathogenesis of the human and ruminant inflammatory bowel disorder.
authors: Cellular Immunotherapy and Molecular Immunodiagnostics, Institute of Research and Technology Thessaly, Larissa, Greece.
authors: Christos
authors: C
authors: Liaskos
authors: Vassiliki
authors: V
authors: Spyrou
authors: Dirk
authors: D
authors: Roggenbuck
authors: Labrini V
authors: LV
authors: Athanasiou
authors: Timoklia
authors: T
authors: Orfanidou
authors: Athanasios
authors: A
authors: Mavropoulos
authors: Dirk
authors: D
authors: Reinhold
authors: Eirini I
authors: EI
authors: Rigopoulou
authors: Georgios S
authors: GS
authors: Amiridis
authors: Charalambos
authors: C
authors: Billinis
authors: Dimitrios P
authors: DP
authors: Bogdanos
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002417:Cattle; D003424:Crohn Disease / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology; D010179:Pancreas / Q000276:immunology*; D010283:Paratuberculosis / Q000276:immunology*; D012418:Ruminants; D016036:Seroepidemiologic Studies; D012756:Sheep
chemical_list: D000907:Antibodies, Bacterial; D001323:Autoantibodies; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D007074:Immunoglobulin G