INTRODUCTION: Immunosuppression, the cornerstone of management of Crohn's disease (CD) and ulcerative colitis (UC) (inflammatory bowel diseases; IBD) is associated with an increased risk of serious infections that is inadequately predicted by clinical risk factors. The role of genetics in determining susceptibility to infections is unknown. METHODS: From a prospective-consented patient registry, we identified IBD patients with serious infections requiring hospitalization. Analysis was performed to identify IBD-related and non-IBD related immune response loci on the Immunochip that were associated with serious infections and a genetic risk score (GRS) representing the cumulative burden of the identified single nucleotide polymorphisms was calculated. Multivariable logistic regression used to identify effect of clinical and genetic factors. RESULTS: The study included 1333 IBD patients (795 CD, 538 UC) with median disease duration of 13 years. A total of 133 patients (10%) had a serious infection requiring hospitalization. Patients with infections were more likely to have CD and had shorter disease duration. The most common infections were skin and soft-tissue, respiratory and urinary tract infections. Eight IBD risk loci and two other polymorphisms were significantly associations with serious infections. Each one point increase in the infection GRS was associated with a 50% increase in risk of infections (OR = 1.53, 95% CI = 1.37-1.70) (p = 1 × 10-14), confirmed on multivariable analysis. Genetic risk factors improved performance of a model predicting infections over clinical covariates alone (p < 0.001). CONCLUSIONS: Genetic risk factors may predict susceptibility to infections in patients with IBD.
INTRODUCTION: Immunosuppression, the cornerstone of management of Crohn's disease (CD) and ulcerative colitis (UC) (inflammatory bowel diseases; IBD) is associated with an increased risk of serious infections that is inadequately predicted by clinical risk factors. The role of genetics in determining susceptibility to infections is unknown. METHODS: From a prospective-consented patient registry, we identified IBD patients with serious infections requiring hospitalization. Analysis was performed to identify IBD-related and non-IBD related immune response loci on the Immunochip that were associated with serious infections and a genetic risk score (GRS) representing the cumulative burden of the identified single nucleotide polymorphisms was calculated. Multivariable logistic regression used to identify effect of clinical and genetic factors. RESULTS: The study included 1333 IBD patients (795 CD, 538 UC) with median disease duration of 13 years. A total of 133 patients (10%) had a serious infection requiring hospitalization. Patients with infections were more likely to have CD and had shorter disease duration. The most common infections were skin and soft-tissue, respiratory and urinary tract infections. Eight IBD risk loci and two other polymorphisms were significantly associations with serious infections. Each one point increase in the infection GRS was associated with a 50% increase in risk of infections (OR = 1.53, 95% CI = 1.37-1.70) (p = 1 × 10-14), confirmed on multivariable analysis. Genetic risk factors improved performance of a model predicting infections over clinical covariates alone (p < 0.001). CONCLUSIONS: Genetic risk factors may predict susceptibility to infections in patients with IBD.
Authors: Mahesh Gajendran; Chandraprakash Umapathy; Priyadarshini Loganathan; Jana G Hashash; Ioannis E Koutroubakis; David G Binion Journal: Dig Dis Sci Date: 2015-09-30 Impact factor: 3.199
Authors: S Noda; K Tanaka; S Sawamura ; M Sasaki; T Matsumoto; K Mikami; Y Aiba; H Hasegawa; N Kawabe; Y Koga Journal: J Immunol Date: 2001-03-01 Impact factor: 5.422
Authors: Mike van der Have; Bas Oldenburg; Herma H Fidder; Tim D G Belderbos; Peter D Siersema; Martijn G H van Oijen Journal: Dig Dis Sci Date: 2013-08-15 Impact factor: 3.199