Significance of serological markers in the disease course of ulcerative colitis in a prospective clinical cohort of patients

PLoS One. 2018 Mar 28;13(3):e0194166. doi: 10.1371/journal.pone.0194166. eCollection 2018.

Abstract

Background & aims: To determine the prognostic potential of classic and novel serologic antibodies regarding unfavorable disease course in a prospective ulcerative colitis (UC) patient cohort, since few and conflicting data are available in the literature regarding this matter.

Methods: 187 consecutive patients were studied prospectively (median follow-up: 135 months) from a single referral IBD center in Hungary. Sera were tested for different IgA/IgG type autoantibodies (anti-neutrophil cytoplasmic [ANCA], anti-DNA-bound-lactoferrin [anti-LFS], anti-goblet cell [anti-GAB] and anti-pancreatic [PAB: anti-CUZD1 and anti-GP2)]) by indirect immunofluorescence technique and for anti-microbial (anti-Saccharomyces cerevisiae [ASCA] IgG/IgA and anti-OMP Plus™ IgA) antibodies by enzyme-linked immunosorbent assays.

Results: A total of 73.6%, 62.4% and 11.2% of UC patients were positive for IgA/IgG type of atypical perinuclear-ANCA, anti-LFS and anti-GAB, respectively. Occurrences of PABs were 9.6%, while ASCA IgA/IgG and anti-OMP IgA were 17.6% and 19.8%, respectively. Antibody status was stable over time. IgA type PABs were more prevalent in patients with primary sclerosing cholangitis (37.5% vs. 4.7% for anti-CUZD1 and 12.5% vs. 0% for anti-GP2, p<0.001 for both). IgA type ASCA and anti-CUZD1 antibodies were associated with higher risk of requirement for long-term immunosuppressant therapy in Kaplan-Meier analysis (pLogRank <0.01 for both). However, in multivariate Cox-regression analysis only ASCA IgA (HR: 2.74, 95%CI: 1.46-5.14, p<0.01) remained independent predictor. UC-related hospitalization due to disease activity was only associated with multiple antibody positivity (for 3 or more; HR 2.03 [95% CI: 1.16-3.56]; p = 0.013). None of the individual antibodies or their combination was associated with the risk of development of extensive disease or colectomy.

Conclusion: Even with low prevalence rates, present study gives further evidence to the role of certain antibodies as markers for distinct phenotype and disease outcome in UC. Considering the result of the multivariate analysis the novel antibodies investigated do not seem to be associated with poor clinical outcome in UC, only a classic antibody, IgA subtype ASCA remained an independent predictor of long-term immunosuppressive therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Colitis, Ulcerative / blood*
  • Colitis, Ulcerative / epidemiology
  • Female
  • Humans
  • Male
  • Prevalence
  • Prospective Studies

Substances

  • Autoantibodies
  • Biomarkers

Associated data

  • figshare/4765102

Grants and funding

Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00426/11), Internal Research Grant (RH/885/2013) of University of Debrecen and Research Grant of University National, Research, Development and Innovation Office (K 115818, 2015/1), IOIBD Research Grant (2012-2015). These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. They only provided financial support in the form of authors’ salaries and/or research materials. Inova Diagnostics, Inc., as a funder provided support in the form of salaries for authors [GLN, ZS] and partially research material (QUANTA Lite® ELISA for the detection of ASCA IgG /IgA and anti-OMP PlusTM antibodies), but the commercial company itself did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript; only the co-authors (GLN, ZS) did.