Crohn's disease-specific anti-CUZD1 pancreatic antibodies are absent in ruminants with paratuberculosis

Christos Liaskos, Vassiliki Spyrou, Labrini V. Athanasiou, Timoklia Orfanidou, Athanasios Mavropoulos, Eirini I. Rigopoulou, Georgios S. Amiridis, Yehuda Shoenfeld, Charalambos Billinis, Dimitrios P. Bogdanos

Research output: Contribution to journalArticlepeer-review


Background: Pancreatic autoantibodies (PABs) specifically recognizing GP2 and/or CUZD1 are present in more than 35% of patients with Crohn's disease (CrD). We have recently provided evidence of the presence of GP2-specific PABs in ruminants with paratuberculosis (ptb), a Mycobacterium avium paratuberculosis (MAP)-induced disease resembling CrD. Objective: To assess whether anti-CUZD1 antibodies are also present in ruminants with ptb. Methods: A total of 110 samples (73 cattle/37 sheep) were studied including 40 with ptb (24 cattle/16 sheep; 20 anti-GP2 antibody pos) and 70 without ptb (49 cattle/21 sheep; 10 anti-GP2 antibody pos). The samples were pre-characterized for anti-MAP and anti-GP2 antibodies by ELISA. Evidence of MAP was confirmed by PCR. Anti-CUZD1 antibody testing was performed by indirect immunofluorescence (IIF) based on transfected HEK293 cells expressing CUZD1. Anti-sheep or anti-cattle specific antisera were used as revealing antibodies. Results: None of the ruminant sera had anti-CUZD1 antibodies by IIF testing at dilutions varying from 1/10 to 1/160. Methodological flaws were prevented by a series of tests. Control sera from anti-CUZD1 positive CrD samples have shown anti-CUZD1 antibody reactivity at various concentrations. Antibody reactivity to GP2-expressing HEK293 cells has confirmed the reactivity to GP2 in ruminant sera found positive for anti-GP2 antibodies by ELISA. Conclusion: The present study has found no evidence of anti-CUZD1 PABs in MAP-induced ptb. Our findings indicate that the induction of CUZD1-specific PABs is unrelated to MAP infection and that the mechanisms responsible for the loss of tolerance to GP2 and CUZD1 are probably quite distinct.

Original languageEnglish
Pages (from-to)384-390
Number of pages7
JournalClinics and Research in Hepatology and Gastroenterology
Issue number3
StatePublished - 1 Jun 2015
Externally publishedYes


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