Genetic risk factors for serious infections in inflammatory bowel diseases.
BACKGROUND
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.
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Saranya
S
Sasidharan
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Vijay
V
Yajnik
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Hamed
H
Khalili
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
John
J
Garber
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Ramnik
R
Xavier
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Ashwin N
AN
Ananthakrishnan
D000328:Adult; D005260:Female; D023281:Genomics; D005838:Genotype; D006760:Hospitalization; D006801:Humans; D007239:Infections / Q000453:epidemiology* / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D014481:United States
Crohn’s disease; Genetics; immunosuppression; infections; pneumonia; sepsis