Wang Yuqing, Xue Huiwen, Olén Ola, Everhov Åsa H, Wei Hui, Liu Qifa, Liu Qianwei
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Clinical Medical Research Center of Hematological Diseases of Guangdong Province, Guangzhou, China.
J Crohns Colitis. 2025 Jul 12. doi: 10.1093/ecco-jcc/jjaf118.
Crohn's disease (CD) is a chronic immune-mediated inflammatory disorder. Its pathophysiology involves dysregulation of both innate and adaptive immune responses, which can occur in clonal hematopoiesis of indeterminate potential (CHIP) individuals. Therefore, we hypothesize that CHIP may influence CD incidence. However, no study has explored the association between CHIP and incident CD. We analyzed UK Biobank data to investigate the association between CHIP and incident CD.
CHIP was defined based on the whole-exome sequencing data. The outcome was incident CD. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for CD in relation to CHIP.
This study included 461,913 participants, of whom 14,339 (3.1%) had CHIP. The incidence rate of CD was 21.6 and 37.7 per 100,000 person-years for individuals without and with CHIP, respectively. We found a statistically significant increased risk of CD among individuals with CHIP (HR: 1.68; 95% CI: 1.30-2.16), compared with the reference group. This association was particularly stronger in individuals with JAK2-mutant CHIP (HR: 7.28; 95% CI: 1.82-29.13), ASXL1-mutant CHIP (HR: 3.07; 95% CI: 1.74-5.44) and DNMT3A-mutant CHIP (HR: 1.73; 95% CI: 1.24-2.42). Additionally, the association did not vary greatly by demographic, socioeconomic, lifestyle factors, CHIP clone size, or cancer comorbidity.
CHIP was associated with a markedly increased risk of subsequent CD. The association was particularly stronger in JAK2-mutant CHIP, ASXL1-mutant CHIP, and DNMT3A-mutant CHIP. The findings of this study may offer potential insights for future investigations into the mechanistic underpinnings of CD.
克罗恩病（CD）是一种慢性免疫介导的炎症性疾病。其病理生理学涉及固有免疫和适应性免疫反应的失调，这在具有不确定潜能的克隆性造血（CHIP）个体中可能会发生。因此，我们推测CHIP可能会影响CD的发病率。然而，尚无研究探讨CHIP与新发CD之间的关联。我们分析了英国生物银行的数据，以研究CHIP与新发CD之间的关联。
基于全外显子测序数据定义CHIP。结局为新发CD。采用Cox回归模型计算与CHIP相关的CD的风险比（HRs）及95%置信区间（CIs）。
本研究纳入461,913名参与者，其中14,339名（3.1%）有CHIP。无CHIP和有CHIP的个体中，CD的发病率分别为每10万人年21.6例和37.7例。与参照组相比，我们发现有CHIP的个体患CD的风险有统计学意义的增加（HR：1.68；95%CI：1.30 - 2.16）。这种关联在携带JAK2突变的CHIP个体（HR：7.28；95%CI：1.82 - 29.13）、携带ASXL1突变的CHIP个体（HR：3.07；95%CI：1.74 - 5.44）和携带DNMT3A突变的CHIP个体（HR：1.73；95%CI：1.24 - 2.42）中尤为明显。此外，该关联在人口统计学、社会经济、生活方式因素、CHIP克隆大小或癌症合并症方面没有很大差异。
CHIP与随后发生CD的风险显著增加相关。这种关联在携带JAK2突变的CHIP、携带ASXL1突变的CHIP和携带DNMT3A突变的CHIP中尤为明显。本研究结果可能为未来对CD发病机制基础的研究提供潜在的见解。
