Trial reportNature immunology2022
Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.
Open access · greenAbstract readClinical Trial
In one paragraph
Trial report in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 26% of its field
What it found
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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
11 citing papers in PubMed, 18 citations in OpenAlex.
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- iRhom2 regulates HMGB1 secretion to modulate inflammation and hepatocyte senescence in an in vitro model of ischemia-reperfusion injury.Cell death & disease · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Pursuing Precision Medicine in Managing Rheumatoid Arthritis.International journal of rheumatic diseases · 2025Review
- The immune health metric as an indicator of health and disease.Nature reviews. Rheumatology · 2024Article
- Targeting iRhom2/ADAM17 attenuates COVID-19-induced cytokine release from cultured lung epithelial cells.Biochemistry and biophysics reports · 2024Article
- Article
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- OTULIN haploinsufficiency predisposes to environmentally directed inflammation.Frontiers in immunology · 2024Article
- P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction.Cell communication and signaling : CCS · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 9 institutions in 4 countries.
Satoshi KuboMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9693-9263
Jill M FritzMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Hayley M Raquer-McKayMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Rhea KatariaMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ivan Vujkovic-CvijinMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8611-4900
Ahmad Al-ShaibiResearch Branch, Sidra Medicine, Doha, Qatar.ORCID http://orcid.org/0000-0002-4345-5772
Yikun YaoMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lixin ZhengMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Juan ZouMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Alex D WaldmanMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2016-6118
Xinyi JingMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Taylor K FarleyMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ann Y ParkMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0130-1521
Andrew J OlerBioinformatics 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 http://orcid.org/0000-0002-6310-0434
Adrian K CharlesDepartment of Anatomical Pathology, Sidra Medicine, Doha, Qatar.ORCID http://orcid.org/0000-0002-3193-1065
Melanie MakhloufResearch Branch, Sidra Medicine, Doha, Qatar.
Eman H AbouMoussaResearch Branch, Sidra Medicine, Doha, Qatar.
Reem HasnahResearch Branch, Sidra Medicine, Doha, Qatar.
Luis R SaraivaResearch Branch, Sidra Medicine, Doha, Qatar.ORCID http://orcid.org/0000-0003-4079-0396
Sundar GanesanBiological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abdulrahman Ahmed Al-SubaieyCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
Helen MatthewsMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Emilio FlanoDiscovery Oncology and Immunology, Merck & Co., Inc., Boston, MA, USA.
Hyun Hee LeeDiscovery Oncology and Immunology, Merck & Co., Inc., Boston, MA, USA.
Alexandra F FreemanLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Asena Pınar SeferDivision of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.
Ersin SayarDepartment of Pediatric Gastroenterology, Altinbas University Medical Park Bahcelievler Hospital, Istanbul, Turkey.
Erkan ÇakırDivision of Pediatric Pulmonology, Department of Pediatrics, Bezmialem Vakif University, School of Medicine, Istanbul, Turkey.
Elif Karakoc-AydinerDivision of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.
Safa BarisDivision of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.ORCID http://orcid.org/0000-0002-4730-9422
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 http://orcid.org/0000-0001-9962-3571
Ahmet OzenDivision of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey. ahmet.ozen@marmara.edu.tr.ORCID http://orcid.org/0000-0002-9065-1901
Bernice LoResearch Branch, Sidra Medicine, Doha, Qatar. blo@sidra.org.ORCID http://orcid.org/0000-0002-1087-6845
Michael J LenardoMolecular Development of the Immune System Section, Laboratory of Immune System Biology and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. lenardo@nih.gov.ORCID http://orcid.org/0000-0003-1584-468X
National Institutes of Health · USMarmara University · TRBoston University · USAltınbaş University · TRBezmiâlem Vakıf Üniversitesi · TRCedars-Sinai Medical Center · USHamad bin Khalifa University · QAMonell Chemical Senses Center · USQatar Airways (Qatar) · QA
Funding
Infectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1MMolecular Mechanisms Of The Autoimmune Lymphoproliferative Syndrome And Other Immunoregulatory DisordersZIAAI000769 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN · 2009 to 2024
$16.7MPrimary Immune Deficiency ClinicZIAAI001247 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FREEMAN, ALEXANDRA · 2019 to 2025
$8.7MRole of Tissue-Specific Factors in the Control of ImmunityZIAAI001132 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2011 to 2025
$6.4MIntramural NIH HHS ZIA AI000769
Abstract
We report a pleiotropic disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in two kindreds with recurrent infections in different organs. One patient had recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement and the other two experienced recurrent respiratory infections. Loss of iRHOM2, a rhomboid superfamily member that regulates the ADAM17 metalloproteinase, caused defective ADAM17-dependent cleavage and release of cytokines, including tumor-necrosis factor and amphiregulin. To understand the diverse clinical phenotypes, we challenged Rhbdf2
Indexed as
A549 CellsADAM17 ProteinAnimalsCarrier ProteinsChildChild, PreschoolCitrobacter rodentiumColitisCytokinesEnterobacteriaceae InfectionsFemaleHEK293 CellsHumansInfant, NewbornMacrophagesMaleADAM17 ProteinAdam17 protein, mouseCarrier ProteinsCytokinesiRhom2 protein, mouse
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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.