Crohn's disease-specific pancreatic autoantibodies are specifically present in ruminants with paratuberculosis: Implications for the pathogenesis of the human disease
AuthorLiaskos, C.; Spyrou, V.; Roggenbuck, D.; Athanasiou, L. V.; Orfanidou, T.; Mavropoulos, A.; Reinhold, D.; Rigopoulou, E. I.; Amiridis, G. S.; Billinis, C.; Bogdanos, D. P.
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 (IF) 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 +/- 25.45D 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.
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