ArticleThe Journal of experimental medicine2025
Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.
Abstract read
In one paragraph
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.
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.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of high-intensity interval training on cardiopulmonary function and quality of life in patients with myocardial infarction: a meta-analysis.Frontiers in cardiovascular medicine · 2025Pooled it
- Hudi enteric-coated capsule and its active constituent polydatin suppress Th1/Th17-mediated intestinal inflammation by modulating the KEAP1-NFE2L2 signaling pathway.Precision clinical medicine · 2026Article
- Editorial comment on "Functional changes in the gut microbiota are associated with the intestinal phenotype in A20 haploinsufficiency".Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
- Allogeneic hematopoietic cell transplantation for partial RAG deficiency in children and adults: Excellent outcomes with a reduced-intensity posttransplantation cyclophosphamide-based approach.The Journal of allergy and clinical immunology · 2026Article
- Bridging Rare to Common Diseases: Precision Medicine and the Transforming Landscape of Pediatric Allergy and Immunology.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
51 authors.
Riccardo Castagnoli *Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0029-9383
Francesca Pala *Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4537-9061
Poorani Subramanian *Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-4371-7290
Cihan Oguz *Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2860-3546
Benjamin SchwarzResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT, USA.ORCID 0000-0002-5894-953X
Ai Ing LimMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-8834-3136
Andrew S BurnsNIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0002-4818-2029
Elena FontanaIRCCS Humanitas Research Hospital , Milan, Italy.ORCID 0000-0001-8853-3335
Marita BosticardoLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-1771-4523
Cristina CorsinoLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0009-0009-9148-4613
Angelina AngelovaBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-2923-0072
Ottavia M DelmonteLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-4772-0799
Heather KenneyLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0009-0006-7009-2547
Deanna RileyLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2440-4195
Grace SmithLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6381-0391
Lisa Ott de BruinWillem-Alexander Children's Hospital, Department of Pediatrics, Pediatric Stem Cell Transplantation Program, Leiden University Medical Center , Leiden, Netherlands.ORCID 0000-0001-5608-2728
Vasileios OikonomouLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-7553-0159
Lucas Dos Santos DiasLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-2344-1354
Danielle FinkNeutrophil Monitoring Lab, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID 0009-0002-6260-9308
Eric BohrnsenResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT, USA.ORCID 0000-0003-4327-5242
Cole D KimzeyResearch Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT, USA.ORCID 0009-0009-5478-7113
Gian Luigi MarsegliaPediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy.ORCID 0000-0003-3662-0159
Guisela Alva-LozadaAllergy and Immunology Division Hospital Nacional Edgardo Rebagliati Martins , Lima, Peru.ORCID 0009-0000-1058-4351
Jenna R E BergersonLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9122-4998
Ana BrettHospital Pediátrico, Unidade Local de Saúde de Coimbra , Coimbra, Portugal.ORCID 0000-0002-6762-3515
Karlla W BrigattiClinic for Special Children , Gordonville, PA, USA.ORCID 0000-0002-9178-815X
Dimana DimitrovaExperimental Transplantation and Immunotherapy Branch, National Cancer Institute of the National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-4868-6852
Cullen M DutmerAllergy and Immunology, Children's Healthcare of Atlanta, Emory University School of Medicine , Atlanta, GA, USA.ORCID 0000-0001-9806-4739
Alexandra F FreemanLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-7005-8345
Hanadys AleDivision of Immunology, Allergy and Rheumatology, Joe DiMaggio Children's Hospital, Memorial Healthcare System, Hollywood, FL, USA.ORCID 0009-0008-4583-1808
Steven M HollandLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-3207-5464
Francesco LicciardiImmuno-reumatologia, Pediatria Specialistica Universitaria, Ospedale Infantile Regina Margherita , Torino, Italy.ORCID 0000-0001-5395-2740
Srdjan PasicDepartment of Pediatric Immunology, Mother and Child Health Institute, Medical Faculty, University of Belgrade, Belgrade, Serbia.ORCID 0000-0001-7761-0024
Laura E PoskittClinic for Special Children , Gordonville, PA, USA.ORCID 0000-0003-0358-2723
David E PottsDivision of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.ORCID 0009-0001-1051-5791
Joseph F DassoDivision of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.ORCID 0000-0001-8917-8603
Svetlana O SharapovaBelarusian Research Center for Pediatric Oncology, Hematology and Immunology , Minsk, Belarus.ORCID 0000-0003-1390-2348
Kevin A StraussClinic for Special Children , Gordonville, PA, USA.ORCID 0000-0002-6429-8657
Brant R WardDivision of Allergy and Immunology, Children's National Hospital, Washington, DC, USA.ORCID 0000-0001-8056-6466
Melis YilmazDivision of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.ORCID 0000-0002-8506-7372
Douglas B KuhnsNeutrophil Monitoring Lab, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID 0000-0002-9971-0760
Michail S LionakisLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4994-9500
Stephen R DaleyCentre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology , Brisbane, Australia.ORCID 0000-0002-5870-644X
Heidi H KongCutaneous Microbiome and Inflammation Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4424-064X
Julia A SegreMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6860-348X
Anna VillaSan Raffaele-Telethon Institute for Gene Therapy (SR-Tiget), IRCSS San Raffaele Scientific Institute , Milan, Italy.ORCID 0000-0003-4428-9013
Stefania PittalugaLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-7688-1439
Jolan E WalterDivision of Pediatric Allergy/Immunology, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
Ivan Vujkovic-CvijinDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID 0000-0002-8611-4900
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-9962-3571
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8335-0262
Funding
Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2MMechanisms driving extrafollicular polyreactive B cell lineages in partial RAG deficiencyR01AI153830 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI WALTER, JOLAN ESZTER · 2021 to 2025
$2.2MGut microbiota-mediated fiber fermentation in HIV-associated cardiovascular diseaseDP1HL174182 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI Ivan Vujkovic-Cvijin · 2024 to 2026
$1.7MCedars-Sinai Medical CenterCrohn's & Colitis Foundation Career Development 831262Fondazione GhislieriHHS HHSN316201300006W/75N93022F00001National Institute of Allergy and Infectious DiseasesNHLBI NIH HHS DP1 HL174182NHLBI NIH HHS DP1HL174182NIAID NIH HHS R01 AI153830NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01DK062413NIH HHS AI001222
Abstract
Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.
Indexed as
Homeodomain ProteinsInflammatory Bowel DiseasesAnimalsBone Marrow TransplantationDisease Models, AnimalFemaleGastrointestinal MicrobiomeHumansMaleMiceMice, Inbred C57BLTh17 CellsT-Lymphocytes, RegulatoryHomeodomain ProteinsRAG-1 protein
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
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.