Functional characterization of DcR3 in EBV transformed cell lines from IBD patients of different allelic background and role in disease pathogenesis

Rahul Pandey,Kelly Kachelries,Robert N Baldassano,Struan Fa Grant,Hakon Hakonarson,Christopher J Cardinale

doi:10.15761/bgg.1000145

Abstract

Functional characterization of DcR3 in EBV transformed cell lines from IBD patients of different allelic background and role in disease pathogenesis

Highlights

Inflammatory Bowel Disease (IBD) collectively refers to 2 major chronic intestinal disorders of unknown etiology, Crohn Disease (CD) and Ulcerative Colitis (UC) and involves an overactive immune component in the intestinal mucosa [1,2]
The study looked for difference in serum Decoy Receptor 3 (DcR3) concentration between individuals with IBD and controls and, within the IBD group, between those with and without the identified at-risk variants captured by the TNFRSF6B tagging SNPs and found that mean serum DcR3 concentration was increased approximately 50fold in individuals with IBD and was highest in those with IBD carrying the minor allelic variant, which is protective of IBD
1×106 cells derived from control and IBD patients EBV transformed cell lines harboring risk variants in TNFRSF6B (A allele) were used in a time course experiment to evaluate the kinetics of IκBα degradation for time points ranging from 0 min to 60 min

Summary

Introduction

Inflammatory Bowel Disease (IBD) collectively refers to 2 major chronic intestinal disorders of unknown etiology, Crohn Disease (CD) and Ulcerative Colitis (UC) and involves an overactive immune component in the intestinal mucosa [1,2] Both disease forms share some clinical and pathological features, the mechanisms underlying inflammation differ between CD and UC [3]. In a GWAS analysis carried out in a cohort of 1,011 individuals with pediatriconset IBD and 4,250 matched controls, we identified and replicated a significantly associated, previously unreported locus on chromosomes 20q13 (rs2315008 [T] and rs4809330 [A]; P = 6.30 × 10−8 and 6.95 × 10−8, respectively; odds ratio (OR) = 0.74 for both) located close to the TNFRSF6B gene [4] Association at this locus continued to strengthen in the recent meta-analyses of Crohn’s disease [5] after confirming replication of the locus. TNFRSF6B encodes for Decoy Receptor 3 (DcR3) protein, which binds to cytokines of the tumor necrosis factor superfamily, Received: August 08, 2019; Accepted: August 16, 2019; Published: August 20, 2019

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