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. 2008 Oct;6(10):1105-11.
doi: 10.1016/j.cgh.2008.04.032. Epub 2008 Jul 10.

Increased immune reactivity predicts aggressive complicating Crohn's disease in children

Marla C Dubinsky  1 , 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, Carol Landers, Kent D Taylor, Stephan R Targan, Jerome I Rotter, James Markowitz, Jeffrey Hyams; Western Regional Pediatric IBD Research Alliance; Pediatric IBD Collaborative Research Group; Wisconsin Pediatric IBD Alliance
Affiliations

Increased immune reactivity predicts aggressive complicating Crohn's disease in children

Marla C Dubinsky et al. Clin Gastroenterol Hepatol. 2008 Oct.

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.

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Conflict of interest statement

Conflict of interest: Marla Dubinsky, MD: consultant Prometheus labs, Stephan R Targan shareholder Prometheus, Carol Landers, shareholder Prometheus Labs, Jeffrey Hyams and James Markowitz, research support Centocor Inc

Study participants aware of any conflict of interest

Figures

Figure 1
Figure 1
Figure 1A: Frequency of non-penetrating non-stricturing disease, internal penetrating disease, stricturing disease and surgery amongst the different antibody sum groups. P trend < 0.0001 Figure 1B: Frequency of non-penetrating non-stricturing disease, internal penetrating disease, stricturing disease and surgery amongst the different quartile sum score groups. P trend < 0.0001
Figure 2
Figure 2
Figure 2A: Survival estimates for internal penetrating and/or stricturing disease by antibody sum 0, vs. 1, vs. 2, vs. 3 (prospective patients only). P value < 0.0001 Figure 2B: Survival estimates for CD related surgery by antibody sum 0, vs. 1, vs. 2, vs. 3 (prospective patients only). P value < 0.0001 Figure 2C: Survival estimates for internal penetrating and/or stricturing disease by quartile sum score (QSS) group 1, vs. 2, vs. 3, vs. 4 (prospective patients only). P value < 0.0001 Figure 2D: Survival estimates for CD related surgery by quartile sum score (QSS) group 1, vs. 2, vs. 3, vs. 4 (prospective patients only). P value < 0.0001
Figure 3
Figure 3
Figure 3A: Survival estimates for internal penetrating and/or stricturing disease by antibody sum 0, vs. 1, vs. 2, vs. 3 (all patients). P value < 0.0001 Figure 3B: Survival estimates for internal penetrating and/or stricturing disease by quartile sum score (QSS) group 1, vs. 2, vs. 3, vs. 4 (all patients). P value < 0.0001 1
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References

    1. Landers CJ, Cohavy O, Misra R, et al. Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. Gastroenterology. 2002;123:689–699. - PubMed
    1. Vasiliauskas EA, Plevy SE, Landers CJ, et al. Perinuclear antineutrophil cytoplasmic antibodies in patients with Crohn's disease define a clinical subgroup. Gastroenterology. 1996;110:1810–1819. - PubMed
    1. Vasiliauskas EA, Kam LY, Karp LC, et al. Marker antibody expression stratifies Crohn's disease into immunologically homogeneous subgroups with distinct clinical characteristics. Gut. 2000;47:487–496. - PMC - PubMed
    1. Mow WS, Vasiliauskas EA, Lin YC, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology. 2004;126:414–424. - PubMed
    1. Targan SR, Landers CJ, Yang H, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. Gastroenterology. 2005;128:2020–2028. - PubMed

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