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Published on: August 7, 2017
Increased immune reactivity predicts aggressive complicating Crohn's disease in children
Marla C Dubinsky1, Subra Kugathasan, Ling Mei
1Department of Pediatrics, IBD Center, Cedars Sinai Medical Center, Los Angeles, California, USA. dubinskym@csmc.edu
Insights
Increased immune reactivity in children with Crohn's disease (CD) is linked to faster disease progression and complications. Identifying high-risk patients early can guide therapy for pediatric CD.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Genetics
Background:
- Crohn's disease (CD) complications in children necessitate early risk identification for effective treatment.
- Understanding the role of immune responses and CARD15 variants in CD progression is crucial.
Purpose of the Study:
- To investigate the association between immune responses (antibody levels) and CARD15 variants with complicated Crohn's disease phenotypes in children.
- To determine if these factors predict disease progression in pediatric CD patients.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure antibodies in 796 pediatric CD cases.
- Genotyping was performed for three CARD15 variants (SNPs 8, 12, and 13).
- Associations between immune markers, CARD15, and clinical outcomes were analyzed.
Main Results:
- 32% of patients developed complications, and 18% required surgery.
- Higher antibody levels correlated significantly with increased risk of internal penetrating disease, stricturing, and surgery.
- Patients with higher immune reactivity showed a significantly faster rate of disease progression.
Conclusions:
- Increased immune reactivity, indicated by antibody levels, is associated with a higher rate of complicated Crohn's disease in children.
- Disease progression is markedly accelerated in pediatric CD patients with heightened immune responses.
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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