Evidence map›Paper›PMID 26836588›Full record

ArticleGastroenterology2016

Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease.

Qi Li, Cheng Hiang Lee, Lauren A Peters, Lucas A Mastropaolo, Cornelia Thoeni, Abdul Elkadri, Tobias Schwerd, Jun Zhu, Bin Zhang, Yongzhong Zhao and 30 more

Open access · bronzeAbstract readCase ReportsMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Review
  7. Current concepts of Helicobacter pylori infection.European journal of medical research · 2025
    Review
  8. Article
  9. Monogenic inflammatory bowel disease: An unfolding enigma.World journal of clinical pediatrics · 2025
    Review
  10. Article
  11. Host-pathobiont interactions in Crohn's disease.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Genetic Variation Between Small Bowel and Colon-Predominant Crohn's Disease.Cellular and molecular gastroenterology and hepatology · 2024
    Article

12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 11 institutions in 5 countries.

Qi LiSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Cheng Hiang LeeGastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia.
Lauren A PetersGraduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Lucas A MastropaoloDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Cornelia ThoeniSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Abdul ElkadriSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Tobias SchwerdTranslational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, University of Oxford and Department of Pediatrics, John Radcliffe Hospital, Oxford, UK.
Jun ZhuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Bin ZhangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Yongzhong ZhaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Ke HaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Antonio DinarzoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Gabriel HoffmanDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Brian A KiddDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Ryan MurchieSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Ziad Al AdhamSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Conghui GuoDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Daniel KotlarzDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
Ernest CutzDivision of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Thomas D WaltersSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Dror S ShouvalDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Mark CurranJanssen R&D, LLC, Spring House, Pennsylvania.
Radu DobrinJanssen R&D, LLC, Spring House, Pennsylvania.
Carrie BrodmerkelJanssen R&D, LLC, Spring House, Pennsylvania.
Scott B SnapperDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology and Hepatology, Brigham & Women's Hospital, Department of Medicine, Boston, Massachusetts.
Christoph KleinDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
John H BrumellSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Mingjing HuGastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia.
Ralph NananGastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia.
Brigitte Snanter-NananGastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia.
Melanie WongImmunology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Francoise Le DeistDepartment of Microbiology and Immunology, CHU Sainte Justine and Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada.
Elie HaddadDepartment of Pediatrics, CHU Sainte-Justine, Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada.
Chaim M RoifmanDivision of Immunology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Colette DeslandresDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada.
Anne M GriffithsSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.
Kevin J GaskinGastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia.
Holm H UhligTranslational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, University of Oxford and Department of Pediatrics, John Radcliffe Hospital, Oxford, UK.
Eric E SchadtDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York.
Aleixo M MuiseSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: aleixo.muise@utoronto.ca.
University of Toronto · CAIcahn School of Medicine at Mount Sinai · USThe University of Sydney · AUCentre Hospitalier Universitaire Sainte-Justine · CAJanssen (United States) · USJohn Radcliffe Hospital · GBLudwig-Maximilians-Universität München · DEBoston Children's Hospital · USBrigham and Women's Hospital · USChildren's Hospital at Westmead · AUHospital for Sick Children · CA

Funding

The Pathogenesis Of Colitis In A Novel Th2 Model Of IBDR01AI050950 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SNAPPER, SCOTT B · 2002 to 2013
$2.6M
Developing methods for curating multi-omics dataU01HG008451 · NHGRI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZHU, JUN · 2015 to 2017
$1.5M
NHGRI NIH HHS U01 HG008451NIAID NIH HHS R01 AI050950
6 · The paper itself

Abstract

BACKGROUND &

aimsSevere forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents.

methodsWe performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture.

resultsWe identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-κB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores.

conclusionsIn WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

Indexed as

Genetic VariationSignal TransductionAge of OnsetAustraliaCells, CulturedComputational BiologyConsanguinityCrohn DiseaseDatabases, GeneticEnglandExomeFemaleGene Expression ProfilingGene Regulatory NetworksGenetic Association StudiesGenetic Predisposition to DiseaseMinor Histocompatibility AntigensNOD2 protein, humanNod2 Signaling Adaptor ProteinRepressor ProteinsTRIM22 protein, humanTripartite Motif ProteinsAntiviral and Antibacterial NetworksNF-kBVEOIBD

Identifiers

PMID26836588
PMCPMC4842103
OpenAlexW2264810876

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.