Related Experiment Video
Updated: Jun 4, 2026
Evaluating Therapeutic Interventions in the SHIP-deficient Mouse Model of Crohn Disease-like Ileitis and Fibrosis
Published on: October 14, 2025
Innate dysfunction promotes linear growth failure in pediatric Crohn's disease and growth hormone resistance in
Sharon D'Mello1, Anna Trauernicht, Anne Ryan
1Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Insights
Pediatric Crohn's disease patients with both CARD15 risk alleles and GM-CSF autoantibodies show impaired growth. This combination also leads to growth hormone resistance in mouse models of ileitis.
Area of Science:
- Pediatric gastroenterology
- Immunology
- Endocrinology
Background:
- Growth failure is a common complication in pediatric Crohn's disease (CD), linked to small bowel involvement and surgery.
- Elevated granulocyte macrophage colony stimulating factor autoantibodies (GM-CSF Ab) correlate with complicated ileal CD requiring surgery.
- This study investigates the combined effect of GM-CSF Ab and CARD15 risk alleles on growth failure and growth hormone resistance.
Purpose of the Study:
- To determine if concurrent GM-CSF Ab and CARD15 risk allele carriage are associated with growth failure in pediatric CD.
- To investigate the impact of these factors on growth hormone resistance in a murine model of ileitis.
Main Methods:
- 229 pediatric CD patients were analyzed for CARD15 genotype, GM-CSF Ab, GH binding protein (GHBP), height (HTz), and weight (WTz) z-scores.
- Murine ileitis was induced in card15-deficient mice via GM-CSF neutralization and NSAID exposure.
- Hepatic GH receptor (GHR) abundance, GH-dependent Stat5 activation, and Igf-I mRNA expression were assessed.
Main Results:
- Patients with concurrent CARD15 risk alleles and GM-CSF Ab (C15(+) GMAb(+)) had reduced height z-scores at diagnosis compared to controls.
- Reduced GHBP in C15(+) GMAb(+) patients suggests decreased GHR abundance.
- Murine models showed reduced hepatic GHR abundance, Stat5 activation, and Igf-I expression.
Conclusions:
- Concurrent genetic variation in CARD15 and GM-CSF autoantibodies contribute to linear growth failure in pediatric CD.
- This combination induces hepatic growth hormone resistance in a murine ileitis model.
Background:
Growth failure remains a common complication of pediatric Crohn's disease (CD) and has been associated with small bowel involvement and need for surgery. We have reported that patients with elevated (≥ 1.6 microg/mL) granulocyte macrophage colony stimulating factor autoantibodies (GM-CSF Ab) are more likely to experience complicated ileal disease requiring surgery. We hypothesized that concurrent GM-CSF Ab and CARD15 risk allele carriage (C15(+) GMAb(+) ) would be associated with growth failure in CD and growth hormone (GH) resistance in murine ileitis.
Methods:
We enrolled 229 pediatric CD patients at two sites and determined CARD15 genotype, serum GM-CSF Ab, and GH binding protein (GHBP), and height (HTz) and weight (WTz) z-scores at diagnosis. Ileitis was induced in card15-deficient mice by GM-CSF neutralization and nonsteroidal antiinflammatory drug (NSAID) exposure. Hepatic GH receptor (GHR) abundance and GH-dependent Stat5 activation were determined by western blot and Igf-I mRNA expression by real-time polymerase chain reaction (PCR).
Results:
Mean (95% confidence interval [CI]) HTz at diagnosis was reduced to -0.48 (-4.2, 2.3) in C15(+) GMAb(+) patients, compared to -0.07 (-4.9, 3.4) in disease controls (P ≤ 0.05). Circulating GHBP, as a marker for tissue GHR abundance, was reduced in C15(+) GMAb(+) patients. Hepatic GHR abundance, GH induction of Stat5 tyrosine phosphorylation, and Igf-I mRNA expression were reduced in male card15-deficient mice with ileitis due to GM-CSF neutralization and NSAID exposure.
Conclusions:
Innate dysfunction due to concurrent genetic variation in CARD15 and neutralizing GM-CSF Ab is associated with linear growth failure in pediatric CD, and hepatic GH resistance in murine ileitis.
More Related Videos
08:50A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
08:37Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
01:18Dysbiosis of the Gut Microbiota
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the colonic...
01:20Inflammatory Bowel Disease IV: Clinical Manifestations