Esai Selvan Myvizhi, Nathan Daniel I, Guisado Daniela, Collatuzzo Giulia, Iruvanti Sushruta, Boffetta Paolo, Mascarenhas John, Hoffman Ronald, Cohen Louis J, Marcellino Bridget K, Gümüş Zeynep H
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, Box 1498, New York, NY 10029, USA.
Tisch Cancer Institute, Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, Box 1079, New York, NY 10029, USA.
Inflamm Bowel Dis. 2025 Jan 6. doi: 10.1093/ibd/izae312.
Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD).
We analyzed whole-exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes.
Older UC patients (age > 45) harbored increased myeloid-CHIP mutations compared to younger patients (age ≤ 45) (P = .01). Lymphoid-CHIP was more prevalent in older IBD patients (P = .007). Young CD patients were found to have myeloid-CHIP with high-risk features. Inflammatory bowel disease patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP (P = .05), while anti-TNF therapy was associated with decreased myeloid-CHIP (P = .03). Pathway enrichment analyses indicated an overlap between CHIP genes, IBD phenotypes, and inflammatory pathways.
Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles, especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease, and acceleration of their inflammatory disease.
不确定潜能克隆性造血（CHIP）是指在无血液系统恶性肿瘤的个体血细胞中，髓系和淋巴系恶性肿瘤基因存在体细胞突变。炎症被认为是CHIP进展为血液系统恶性肿瘤的关键介质，且CHIP患者炎症性疾病的患病率较高。本研究旨在确定炎症性肠病（IBD）患者中CHIP的患病率及特征。
我们分析了587例克罗恩病（CD）、441例溃疡性结肠炎（UC）和293例非IBD对照的全外显子测序数据，以评估CHIP患病率，并使用逻辑回归研究其与临床结局的关联。
与年轻UC患者（年龄≤45岁）相比，老年UC患者（年龄>45岁）的髓系CHIP突变增加（P = 0.01）。淋巴系CHIP在老年IBD患者中更为普遍（P = 0.007）。发现年轻CD患者存在具有高危特征的髓系CHIP。与对照相比，患有CHIP的炎症性肠病患者表现出独特的突变谱。使用类固醇与CHIP增加相关（P = 0.05），而抗TNF治疗与髓系CHIP减少相关（P = 0.03）。通路富集分析表明CHIP基因、IBD表型和炎症通路之间存在重叠。
我们的研究结果强调了IBD与CHIP病理生理学之间的联系。患有IBD和CHIP的患者具有独特的风险特征，尤其是在老年UC患者和年轻CD患者中。这些发现提示IBD中CHIP存在不同的进化途径，IBD医疗服务提供者和血液学家有必要提高认识，以识别可能有CHIP相关并发症风险的患者，包括恶性肿瘤、心血管疾病以及炎症性疾病的加速进展。
