Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children

Marla C. Dubinsky, Subra Kugathasan, Ling Mei, Yoana Picornell, Justin Nebel, Iwona Wrobel, Antonio Quiros, Gary Silber, Ghassan Wahbeh, Lirona Katzir, Eric Vasiliauskas, Ron Bahar, Anthony Otley, David Mack, Jonathan Evans, Joel Rosh, Maria Oliva Hemker, Neal Leleiko, Wallace Crandall, Christine LangtonCarol Landers, Kent D. Taylor, Stephan R. Targan, Jerome I. Rotter, James Markowitz, Jeffrey Hyams

Research output: Contribution to journalArticle

Abstract

Background & Aims: The ability to identify children with CD who are at highest risk for rapid progression from uncomplicated to complicated phenotypes would be invaluable in guiding initial therapy. The aims of this study were to determine whether immune responses and/or CARD15 variants are associated with complicated disease phenotypes and predict disease progression. Methods: Sera were collected from 796 pediatric CD cases and tested for anti-Cbir1 (flagellin), anti-outer membrane protein C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibody by using enzyme-linked immunosorbent assay. Genotyping (Taqman MGB) was performed for 3 CARD15 variants (single nucleotide polymorphisms 8, 12, and 13). Associations between immune responses (antibody sum and quartile sum score, CARD15, and clinical phenotype were evaluated. Results: Thirty-two percent of patients developed at least 1 disease complication within a median of 32 months, and 18% underwent surgery. The frequency of internal penetrating, stricturing, and surgery significantly increased (P trend < .0001 for all 3 outcomes) with increasing antibody sum and quartile sum score. Nine percent of seropositive groups had internal penetrating/stricturing versus 2.9% in the seronegative group (P = .01). Twelve percent of seropositive groups underwent surgery versus 2% in the seronegative group (P = .0001). The highest antibody sum group (3) and quartile sum score group (4) demonstrated the most rapid disease progression (P < .0001). Increased hazard ratio was observed for antibody sum group 3 (7.8; confidence interval, 2.2-28.7), P < .002 and quartile sum score group 4 (11.0; confidence interval, 1.5-83.0, P < .02). Conclusions: The rate of complicated CD increases in children as the number and magnitude of immune reactivity increase. Disease progression is significantly faster in children expressing immune reactivity.

Original languageEnglish (US)
Pages (from-to)1105-1111
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Dubinsky, M. C., Kugathasan, S., Mei, L., Picornell, Y., Nebel, J., Wrobel, I., Quiros, A., Silber, G., Wahbeh, G., Katzir, L., Vasiliauskas, E., Bahar, R., Otley, A., Mack, D., Evans, J., Rosh, J., Hemker, M. O., Leleiko, N., Crandall, W., ... Hyams, J. (2008). Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children. Clinical Gastroenterology and Hepatology, 6(10), 1105-1111. https://doi.org/10.1016/j.cgh.2008.04.032