性结肠炎的多基因风险评分预测了免疫检查点抑制剂介导的结肠炎
Pooja Middha1, Rohit Thummalapalli2, Michael J Betti3
1Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nature communications
|March 27, 2024
概括
通过多基因风险得分 (PRS_UC) 测量性结肠炎 (UC) 的遗传易感性,预测癌症患者的免疫检查点抑制剂介导性结肠炎 (IMC). 这一发现可能有助于识别在免疫治疗期间患IMC风险较高的个体.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 免疫检查点抑制剂 (ICI) 可以引起免疫检查点抑制剂媒介性结肠炎 (IMC),这是一个频繁的不良事件.
- 对诸如克罗恩病 (CD) 和性结肠炎 (UC) 等炎症性肠病的遗传倾向可能会影响IMC风险.
研究的目的:
- 调查是否对克罗恩病 (CD) 和性结肠炎 (UC) 的遗传易感性使个人易患IMC.
- 开发和验证CD (PRSCD) 和UC (PRSUC) 的多基因风险评分 (PRS),以预测IMC风险.
主要方法:
- 在没有癌症的个体中开发了PRSCD和PRSUC.
- 在ICI治疗的非小细胞肺癌 (n=1316) 和胰腺癌患者 (n=873) 的队列中测试了PRSUC和PRSCD.
- 进行了元分析,以评估PRS和IMC发病率和严重程度之间的关联.
主要成果:
- PRSUC显著预测了所有级别的IMC (ORmeta=1.35,P=2×10-03) 和严重的IMC (ORmeta=1.49,P=9×10-04).
- PRSCD没有显示与IMC有任何关联.
- 在接受组合ICI (ORmeta=2.20,P=0.03) 的患者中,PRSUC预测了严重的IMC.
结论:
- PRS_UC可以识别接受ICI治疗的患者,这些患者患IMC的风险增加.
- 使用PRS_UC可能有助于患者监测,并可能改善接受ICI治疗的患者的治疗结果.
相关概念视频
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
179
Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
179
01:29Drugs for Treatment of Ulcerative Colitis in IBD
138
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
138
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
331
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
331
01:30Peptic Ulcer Disease I: Introduction
168
Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
168
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
162
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
162
01:30Inflammatory Bowel Disease II: Crohn's Disease
233
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
233