抗程序性死亡受体1相关性结肠炎临床特征和肠道菌群分析  

Clinical characteristics and microbiome analysis in patients with anti-programmed cell death protein 1 related colitis

作　　者：谭蓓[1] 唐颢[2] 任新渝 周炜洵[3] 钱家鸣[1] 张力[4] 张晓彤[4] Tan Bei;Tang Hao;Ren Xinyu;Zhou Weixun;Qian Jiaming;Zhang Li;Zhang Xiaotong(Department of Gastroenterology,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Internal Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China;Department of Respiratory and Critical Care Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院消化内科,100730 [2]中国医学科学院,北京协和医学院,北京协和医院内科,100730 [3]中国医学科学院,北京协和医学院,北京协和医院病理科,100730 [4]中国医学科学院,北京协和医学院,北京协和医院呼吸与危重症医学科,100730

出　　处：《中华内科杂志》2020年第11期887-893,共7页Chinese Journal of Internal Medicine

基　　金：北京市自然科学基金(7192172)。

摘　　要：目的动态监测分析抗程序性死亡受体1(PD-1)相关性结肠炎患者,治疗过程中临床特征和肠道菌群变化情况。方法分析2019年1月至2020年1月2例非小细胞肺癌患者发生抗PD-1相关性结肠炎的病例系列研究,比较治疗前、治疗后和病情复发时临床症状、内镜和病理表现,以及肠道菌群构成变化。结果患者年龄分别为63岁和69岁,均为男性,临床主要表现为腹泻、炎性指标升高,内镜下结肠弥漫性充血水肿伴糜烂,病理示隐窝结构改变,糖皮质激素治疗有效,可达到临床缓解和黏膜愈合。肠道菌群在激素治疗前、治疗后和病情复发可操作性分类单元组成存在差异。激素治疗后α多样性observed species和Shannon、Simpson、Chao1、ACE指数均下降,菌门水平拟杆菌门增加,厚壁菌门减少,菌属水平拟杆菌属增加,瘤胃菌属减少,乳酸杆菌属为潜在有益菌属。结论抗PD-1相关性结肠炎患者治疗过程中存在临床表现、炎性指标、内镜和病理表现相应变化,同时存在肠道菌群多样性、主要菌门和菌属相对丰度变化。Objective To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis.Methods Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020.The clinical symptoms,endoscopic and pathological manifestations,as well microbiome changes were analyzed and compared during pre-treatment,post-treatment and relapse.Results The main clinical manifestations included diarrhea,elevated inflammatory indicators,colonic mucosal diffuse hyperemic edema with erosion by endoscopy.Changes in the structure of crypts were common pathological characteristics.Glucocorticoids were effective agents,which achieved clinical remission and mucosal healing.The microbiome composition of OTUs was different.After glucocorticoid treatment,the alpha diversity Observed species,Shannon,Simpson,Chao1,ACE indexes all decreased.The Firmicutes decreased with Bacteroidetes increasing in phylum level;while the Bacteroides increased with Ruminococcaceae decreasing in genus level.Lactobacillus was the potentially beneficial genus.Conclusion Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations.Glucocorticoids are effective treatment.The fecal microbiome diversity,relative abundance of major phylum and genus have changed after treatment.

关 键 词：抗程序性死亡受体1 结肠炎 临床特征 肠道菌群 

分 类 号：R574.62[医药卫生—消化系统]