Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children

Elizabeth A. Spencer, Sonia M. Davis, David R. Mack, Brendan M. Boyle, Anne M. Griffiths, Neal S. Leleiko, Cary G. Sauer, David J. Keljo, James F. Markowitz, Susan S. Baker, Joel R. Rosh, Robert N. Baldassano, Maria Oliva-Hemker, Marian D. Pfefferkorn, Anthony R. Otley, Melvin B. Heyman, Joshua D. Noe, Ashish S. Patel, Paul A. Rufo, Keith BenkovJonathan Evans, Stephen Guthery, Michael Kappelman, Dedrick Moulton, Jennifer Strople, Boris Sudel, Prateek Wali, David Ziring, Vin Tangpricha, M. Alison Marquis, Thomas D. Walters, Margaret H. Collins, Subra Kugathasan, Lee A. Denson, Jeffrey S. Hyams, Marla C. Dubinsky

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Original languageEnglish (US)
Pages (from-to)1335-1343
Number of pages9
JournalInflammatory bowel diseases
Volume24
Issue number6
DOIs
StatePublished - May 18 2018

Bibliographical note

Funding Information:
Author Contributions: ES, SD, TW, MC, SK, LD, JH and MD conceived and designed the study. DM, BB, AG, NL, CS, DK, JM, SB, JR, RB, MOH, MP, AO, MH, JN, AS, PR, TW, SK, LD, JH, MD and the PROTECT Study Group acquired data. All authors except the PROTECT Study Group analyzed and interpreted data. ES, SD, AG, NL, JM, TW, SK, LD, JH, and MD drafted the manuscript. All authors except the PROTECT Study Group critically revised the manuscript for important intellectual content. Davis and Marquis performed statistical analysis. Supported by NIDDK 5U01DK095745.

Funding Information:
From the *Icahn School of Medicine, Mount Sinai Hospital, New York, New York, USA; †Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina, USA; ‡Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada; §Nationwide Children’s Hospital, Columbus, Ohio, USA; ¶University of Toronto, Toronto, Ontario, Canada; **Hasbro Children’s Hospital, Providence, Rhode Island, USA; ††Emory University, Atlanta, Georgia, USA; ‡‡Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA; §§Northwell Health, New York, New York, USA; ¶¶University of Buffalo, Buffalo, New York, USA; ***Goryeb Children’s Hospital, Morristown, New Jersey, USA; †††Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; ‡‡‡Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; §§§Riley Children’s, Indiana University, Carmel, Indiana, USA; ¶¶¶Dalhousie University, Halifax, Nova Scotia, Canada; ****University of California at San Francisco, San Francisco, California, USA; ††††Medical College of Wisconsin, Milwaukee, Wisconsin, USA; ‡‡‡‡UT Southwestern, Dallas, Texas, USA; §§§§Boston Children’s Hospital, Boston, Massachusetts, USA; ¶¶¶¶Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; *****Connecticut Children’s Medical Center, Hartford, Connecticut, USA Conflicts of interest: ES has no conflicts to declare. SD is on the independent data monitoring committee at Lycera Corporation. DM is the owner of and has shares in Biotagenics. BB has no conflicts to declare. AM receives research support from and is a consultant for Abbvie. AM is also a consultant for Janssen, Merck, and Takeda and is a speaker for Abbvie and Janssen. NL is a consultant for Abbvie. CG is a consultant for Abbvie. DK has no conflicts to declare. JM is a consultant for Janssen, UCB and Lilly. SB has no conflicts to declare. JR received grant funding from Janssen and Abbvie, in addition to being a consultant for Abbvie, Janssen, Luitpold and UCB. RB has no conflicts to declare. MOH has research grants from Abbvie Immunology and Janssen and does consulting for Hoffman Laroche. MP has no conflicts to declare. AO is on the advisory board of Janssen and Abbvie and receives research support from Abbvie, Janssen, Shire and Astellas. MH has received research grants from Genentech, AbbVie, Sucampo and Janssen. JN has no conflicts to declare. AP is on the speaker’s bureau for Abbvie. PR is a consultant for Shire and Leutpold and a speaker for Abbvie and receives research support from TechLab. MAM and TW have no conflicts to declare. MC is a consultant for Shire, Regeneron, Adare and Receptos and has received research grants from Shire, Regeneron and Receptos. SK is a consultant for Janssen and UCB. LD has received grant support from Abbvie and Janssen. JH is on the advisory board for Janssen and a consultant for Abbvie, Takeda, Lilly, Boerhinger-Ingelheim, Allergan, Pfizer and Astra Zeneca. MD is a consultant for Abbvie, Boehringer-Ingelheim, Celgene, Genetech, Janssen, Pfizer, Prometheus Labs, Salix, Shire, Takeda and UCB.

Publisher Copyright:
© 2018 Crohn's & Colitis Foundation. Published by Oxford University Press. All rights reserved.

Keywords

  • CBir1
  • PROTECT
  • pANCA
  • serologies
  • ulcerative colitis

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