Sasidharan Saranya, Yajnik Vijay, Khalili Hamed, Garber John, Xavier Ramnik, Ananthakrishnan Ashwin N
a Division of Gastroenterology , Massachusetts General Hospital and Harvard Medical School , Boston , MA , USA.
Scand J Gastroenterol. 2017 May;52(5):570-576. doi: 10.1080/00365521.2017.1286381. Epub 2017 Feb 5.
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.
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.
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), confirmed on multivariable analysis. Genetic risk factors improved performance of a model predicting infections over clinical covariates alone (p < 0.001).
Genetic risk factors may predict susceptibility to infections in patients with IBD.
免疫抑制是克罗恩病（CD）和溃疡性结肠炎（UC）（炎症性肠病；IBD）治疗的基石，但与严重感染风险增加相关，而临床风险因素对其预测并不充分。基因在决定感染易感性方面的作用尚不清楚。
从一个前瞻性同意的患者登记处，我们识别出因严重感染需要住院治疗的IBD患者。进行分析以识别免疫芯片上与严重感染相关的IBD相关和非IBD相关免疫反应基因座，并计算代表已识别单核苷酸多态性累积负担的遗传风险评分（GRS）。使用多变量逻辑回归来识别临床和遗传因素的影响。
该研究纳入了1333例IBD患者（795例CD，538例UC），疾病中位病程为13年。共有133例患者（10%）发生了需要住院治疗的严重感染。感染患者更可能患有CD且病程较短。最常见的感染是皮肤和软组织、呼吸道及尿路感染。八个IBD风险基因座和另外两个多态性与严重感染显著相关。感染GRS每增加一分，感染风险增加50%（OR = 1.53，95% CI = 1.37 - 1.70）（p = 1×10），多变量分析证实了这一点。遗传风险因素单独比临床协变量能更好地预测感染模型的表现（p < 0.001）。
遗传风险因素可能预测IBD患者的感染易感性。
