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Merck

Human β-Defensin 2 in Primary Sclerosing Cholangitis.

Clinical and translational gastroenterology (2017-03-17)
Cindy Chang, Ana Lleo, Anchasa Kananurak, Fabio Grizzi, Koichi Tsuneyama, Pietro Invernizzi, Charles L Bevins, Christopher L Bowlus
ABSTRACT

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts frequently associated with inflammatory bowel disease (IBD), suggesting an important role for the gut-liver axis. Defensins are small (3.5-4.5 kDa) anti-microbial peptides that contribute to innate immunity at mucosal surfaces and have been implicated in IBD. The aim of this study was to investigate copy number variation of the gene (DEFB4) encoding human β-defensin 2 (HBD2) and protein expression of HBD2 in PSC. US and Italian PSC cases and unaffected controls (US PSC patients n=89, US controls n=87; Italian PSC patients n=46, Italian controls n=84) were used to estimate HBD2 gene copy number by both quantitative real-time PCR and paralog ratio test. Serum levels of HBD2 were measured by enzyme-linked immunosorbent assay and liver expression was analyzed by immunohistochemistry. Mean serum levels of HBD2 were significantly greater in PSC (1,086±1,721 ng/μl) compared with primary biliary cholangitis (544±754 ng/μl), ulcerative colitis (417±506 ng/μl), and healthy controls (514±731 ng/μl) (P=0.02). However, no significant differences between the frequencies of high DEFB4 gene copy number, defined by >4 copies, and PSC were found in the US, Italian, or combined cohorts. Importantly, a high number of biliary ducts were found immunopositive in PSC samples compared with controls. Our data show that HBD2 serum levels and tissue expression are increased in PSC subjects, suggesting that this arm of innate immunity may be important in the etiopathogenesis of PSC.

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Human Random Control DNA Panel, Panel 1
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