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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures
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
Mahasish Shome, Lusheng Song, Stacy Williams, Yunro Chung, Vel Murugan, Jin G Park, Joshua LaBaer, Ji Qiu, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ 85281, United States
William Faubion, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, United States
Shabana F Pasha, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Scottsdale, AZ 85259, United States
Jonathan A Leighton, Division of Gastroenterology, Mayo Clinic School of Medicine, Scottsdale, AZ 85259, United States
Author contributions: Shome M and Song L designed and ran the experiment; Williams S and Chung Y performed the statistical analysis; Murugan V and Park JG helped in preparation of clones; Faubion W, Pasha SF and Leighton JA provided the serum samples and also provided intellectual guidance; LaBaer J and Qiu J supervised the project and secured funding; Shome M and Qiu J wrote the original manuscript which was then reviewed by remaining authors.
Institutional review board statement: The authors have taken appropriate steps to protect the rights and welfare of humans participating as subjects in the research (IRB Application #: 13-008267).
Informed consent statement: All study participants or their legal guardian of the study provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data from this study is available on request from the corresponding author.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ji Qiu, PhD, Research Assistant Professor, Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 1001 S McAllister Avenue, Tempe, AZ 85281, United States. ji.qiu@asu.edu
Received: April 4, 2022
Peer-review started: April 4, 2022
First decision: May 29, 2022
Revised: June 16, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 14, 2022
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 anti-microbial 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 diagnosis of IBD.
Core Tip: We performed the largest serological profiling of anti-microbial antibodies to date in using 100 Crohn’s disease (CD) and 100 ulcerative colitis (UC) patients. We identified novel anti-microbial antibodies with differential prevalence in inflammatory bowel disease (IBD) patients compared with healthy controls. There was minimal correlation between anti-microbial antibodies and our previously reported autoantibodies in CD patients. We combined novel anti-microbial antibodies to build biomarker panels distinguishing CD vs control, UC vs control and CD vs UC with an area under the curve of 0.81, 0.87, and 0.82, respectively. Subgroup analysis revealed that IBD patients with severe disease had the highest antibody prevalence.
