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 Langton & 6 others Carol Landers, Kent D. Taylor, Stephan R. Targan, Jerome I. Rotter, James Markowitz, Jeffrey Hyams

Research output: Contribution to journalArticle

177 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Crohn Disease
Disease Progression
Phenotype
Antibodies
Confidence Intervals
Antineutrophil Cytoplasmic Antibodies
Antibody Formation
Single Nucleotide Polymorphism
Saccharomyces cerevisiae
Enzyme-Linked Immunosorbent Assay
Pediatrics
Serum
Therapeutics
CBir1 flagellin
OmpC protein

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Dubinsky, M. C., Kugathasan, S., Mei, L., Picornell, Y., Nebel, J., Wrobel, I., ... 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
Dubinsky, Marla C. ; Kugathasan, Subra ; Mei, Ling ; Picornell, Yoana ; Nebel, Justin ; Wrobel, Iwona ; Quiros, Antonio ; Silber, Gary ; Wahbeh, Ghassan ; Katzir, Lirona ; Vasiliauskas, Eric ; Bahar, Ron ; Otley, Anthony ; Mack, David ; Evans, Jonathan ; Rosh, Joel ; Hemker, Maria Oliva ; Leleiko, Neal ; Crandall, Wallace ; Langton, Christine ; Landers, Carol ; Taylor, Kent D. ; Targan, Stephan R. ; Rotter, Jerome I. ; Markowitz, James ; Hyams, Jeffrey. / Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children. In: Clinical Gastroenterology and Hepatology. 2008 ; Vol. 6, No. 10. pp. 1105-1111.
@article{368354ada6ec4cbfb9ad4b2fbb2adf09,
title = "Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children",
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.",
author = "Dubinsky, {Marla C.} and Subra Kugathasan and Ling Mei and Yoana Picornell and Justin Nebel and Iwona Wrobel and Antonio Quiros and Gary Silber and Ghassan Wahbeh and Lirona Katzir and Eric Vasiliauskas and Ron Bahar and Anthony Otley and David Mack and Jonathan Evans and Joel Rosh and Hemker, {Maria Oliva} and Neal Leleiko and Wallace Crandall and Christine Langton and Carol Landers and Taylor, {Kent D.} and Targan, {Stephan R.} and Rotter, {Jerome I.} and James Markowitz and Jeffrey Hyams",
year = "2008",
month = "10",
day = "1",
doi = "10.1016/j.cgh.2008.04.032",
language = "English (US)",
volume = "6",
pages = "1105--1111",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "10",

}

Dubinsky, MC, 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, MO, Leleiko, N, Crandall, W, Langton, C, Landers, C, Taylor, KD, Targan, SR, Rotter, JI, Markowitz, J & Hyams, J 2008, 'Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children', Clinical Gastroenterology and Hepatology, vol. 6, no. 10, pp. 1105-1111. https://doi.org/10.1016/j.cgh.2008.04.032

Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children. / Dubinsky, Marla C.; Kugathasan, Subra; Mei, Ling; Picornell, Yoana; Nebel, Justin; Wrobel, Iwona; Quiros, Antonio; Silber, Gary; Wahbeh, Ghassan; Katzir, Lirona; Vasiliauskas, Eric; Bahar, Ron; Otley, Anthony; Mack, David; Evans, Jonathan; Rosh, Joel; Hemker, Maria Oliva; Leleiko, Neal; Crandall, Wallace; Langton, Christine; Landers, Carol; Taylor, Kent D.; Targan, Stephan R.; Rotter, Jerome I.; Markowitz, James; Hyams, Jeffrey.

In: Clinical Gastroenterology and Hepatology, Vol. 6, No. 10, 01.10.2008, p. 1105-1111.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased Immune Reactivity Predicts Aggressive Complicating Crohn's Disease in Children

AU - Dubinsky, Marla C.

AU - Kugathasan, Subra

AU - Mei, Ling

AU - Picornell, Yoana

AU - Nebel, Justin

AU - Wrobel, Iwona

AU - Quiros, Antonio

AU - Silber, Gary

AU - Wahbeh, Ghassan

AU - Katzir, Lirona

AU - Vasiliauskas, Eric

AU - Bahar, Ron

AU - Otley, Anthony

AU - Mack, David

AU - Evans, Jonathan

AU - Rosh, Joel

AU - Hemker, Maria Oliva

AU - Leleiko, Neal

AU - Crandall, Wallace

AU - Langton, Christine

AU - Landers, Carol

AU - Taylor, Kent D.

AU - Targan, Stephan R.

AU - Rotter, Jerome I.

AU - Markowitz, James

AU - Hyams, Jeffrey

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=52949145981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52949145981&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2008.04.032

DO - 10.1016/j.cgh.2008.04.032

M3 - Article

VL - 6

SP - 1105

EP - 1111

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 10

ER -