Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures  

作　　者：Mahasish Shome Lusheng Song Stacy Williams Yunro Chung Vel Murugan Jin G Park William Faubion Shabana F Pasha Jonathan A Leighton Joshua LaBaer Ji Qiu 

机构地区：[1]Virginia G.Piper Center for Personalized Diagnostics,Biodesign Institute,Arizona State University,Tempe,AZ 85281,United States [2]Department of Internal Medicine,Mayo Clinic,Rochester,MN 55902,United States [3]Department of Internal Medicine,Division of Gastroenterology and Hepatology,Mayo Clinic Arizona,Scottsdale,AZ 85259,United States [4]Division of Gastroenterology,Mayo Clinic School of Medicine,Scottsdale,AZ 85259,United States

出　　处：《World Journal of Gastroenterology》2022年第30期4089-4101,共13页世界胃肠病学杂志（英文版）

摘　　要：BACKGROUND The healthcare burden of inflammatory bowel disease(IBD)is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODS We performed serological profiling of 100 Crohn’s disease(CD)patients,100 ulcerative colitis(UC)patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays.The study subjects were randomly divided into discovery(n=150)and validation(n=150)sets.Statistical analysis was performed using R packages.RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses.We identified novel antibodies against the antigens of Bacteroidetes vulgatus(BVU_0562)and Streptococcus pneumoniae(SP_1992)showing higher prevalence in CD patients relative to healthy controls.We also identified antibodies against the antigen of Streptococcus pyogenes(SPy_2009)showing higher prevalence in healthy controls relative to UC patients.Using these novel antibodies,we built biomarker panels with area under the curve(AUC)of 0.81,0.87,and 0.82 distinguishing CD vs control,UC vs control,and CD vs UC,respectively.Subgroup analysis revealed that penetrating CD behavior,colonic CD location,CD patients with a history of surgery,and extensive UC exhibited highest antibody prevalence among all patients.We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of antimicrobial antibody response in IBD.These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and,after future validation,should aid early and accurate

关 键 词：Inflammatory bowel disease Anti-microbial antibody Protein microarray Crohn’s disease Ulcerative colitis Gut microbiome 

分 类 号：R574.62[医药卫生—消化系统]