ArticleThe Journal of experimental medicine2023
Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
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Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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22citing papers in PubMed, 1 pooled it
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22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Allogeneic hematopoietic cell transplantation is curative in CARMIL2 deficiency.Journal of human immunity · 2026Article
- Primary atopic disorders: Monogenic insights into immunity.Journal of human immunity · 2026Review
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Iparomlimab and tuvonralimab (QL1706) combined definitive chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (QL1706-IIT-02): a single arm, phase 2 trial.EClinicalMedicine · 2026Article
- Celiac Disease as A Gastrointestinal Manifestation in A Patient withEuropean journal of case reports in internal medicine · 2026Article
- Phantom of the immunologic opera: Unmasking the role of innate lymphoid cells (ILC) in inborn errors of immunity (IEI).Journal of human immunity · 2025Review
- A CARMIL2 gain-of-function mutation suffices to trigger most CD28 costimulatory functions in vivo.The Journal of experimental medicine · 2025Article
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- Genomic profiling at a single center cracks the code in inborn errors of immunity.Internal and emergency medicine · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Recurrent eosinophilia with a novel homozygous ARPC1B mutation.Frontiers of medicine · 2025Article
- Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.Immunity · 2024Article
- IL-7-dependent and -independent lineages of IL-7R-dependent human T cells.The Journal of clinical investigation · 2024Article
- DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.Journal of clinical immunology · 2024Article
- Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?Molecular and cellular pediatrics · 2024Review
- A NovelJournal of fungi (Basel, Switzerland) · 2024Article
- Article
- Pathogenesis of autoimmune disease.Nature reviews. Nephrology · 2023Review
- Inborn errors of human B cell development, differentiation, and function.The Journal of experimental medicine · 2023Review
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Authors and funding
83 authors at 20 institutions in 14 countries.
Romain Lévy *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-6393-0198
Florian Gothe *Dept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0003-0421-6610
Mana Momenilandi *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-5340-2762
Thomas Magg *Dept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0003-0158-7790
Marie Materna *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0003-2145-5285
Philipp Peters *Dept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0002-7395-8602
Johannes Raedler *Dept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0003-0979-7274
Quentin PhilippotLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0003-3429-9605
Anita Lena Rack-HochDept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0001-6942-407X
David LanglaisDept. of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID 0000-0003-4429-0110
Mathieu BourgeyDept. of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID 0000-0002-8432-834X
Anna-Lisa LanzDept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0002-2933-1167
Masato OgishiSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0003-2421-7389
Jérémie RosainLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-2822-161X
Emmanuel MartinImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0003-4211-7373
Sylvain LatourImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0001-8238-4391
Natasha VladikineLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-0607-9202
Marco DistefanoLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0001-5069-1194
Taushif KhanResearch Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-7917-8965
Franck RapaportSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0001-6553-2110
Marian S SchulzDept. of Women and Child Health, Hospital for Children and Adolescents, Hospitals University of Leipzig, Leipzig, Germany.ORCID 0000-0003-3032-9512
Ursula HolzerChildren's Hospital, University of Tübingen, Tübingen, Germany.ORCID 0000-0002-2424-4654
Anders FasthDept. of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.ORCID 0000-0002-0033-740X
Georgios SogkasDept. of Immunology and Rheumatology, Medical School Hannover, Hanover, Germany.ORCID 0000-0003-0855-2945
Carsten SpeckmannDept. of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology and Center for Chronic Immunodeficiency (CCI), Institute for Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID 0000-0002-6217-1556
Arianna TroiloDept. of Rheumatology and CCI for Chronic Immunodeficiency, Division of Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID 0000-0001-7229-3058
Venetia BigleyTranslational and Clinical Research Institute and NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.ORCID 0000-0002-3017-2474
Anna RoppeltDept. of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.ORCID 0000-0001-5132-1267
Yael Dinur-SchejterDept. of Bone Marrow Transplantation, Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.ORCID 0000-0003-3332-2391
Ori TokerFaculty of Medicine, Hebrew University of Jerusalem, The Allergy and Clinical Immunology Unit, Shaare Zedek Medical Center, Jerusalem, Israel.ORCID 0000-0002-5248-3193
Karen Helene Bronken MartinsenDept. of Pediatric Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-9040-3134
Roya SherkatAcquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.ORCID 0000-0002-8574-2091
Ido SomekhDept. of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.ORCID 0000-0003-0171-8682
Raz SomechThe Institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel, and The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.ORCID 0000-0001-6648-9425
Dror S ShouvalThe Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel; The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel; Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID 0000-0001-5980-2954
Jörn-Sven KühlDept. of Women and Child Health, Hospital for Children and Adolescents, Hospitals University of Leipzig, Leipzig, Germany.ORCID 0000-0002-1739-1090
Winnie IpDept. of Immunology, Great Ormond Street Hospital, London, UK.ORCID 0000-0002-1550-4856
Elizabeth M McDermottDept. of Pediatrics, Nottingham University Hospitals NHS Trust, Nottingham, UK.ORCID 0000-0003-2381-9513
Lucy CliffeDept. of Pediatrics, Nottingham University Hospitals NHS Trust, Nottingham, UK.ORCID 0000-0002-1375-7067
Ahmet OzenDept. of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.ORCID 0000-0002-9065-1901
Safa BarisDept. of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.ORCID 0000-0002-4730-9422
Hemalatha G RangarajanDivision of Hematology, Oncology and Bone Marrow Transplant, Dept. of Pediatrics, Nationwide Children's Hospital, Columbus, OH.ORCID 0000-0003-3371-2920
Emmanuelle JouanguyLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-7358-9157
Anne PuelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0003-2603-0323
Jacinta BustamanteLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-3439-2482
Marie-Alexandra AlyanakianDept. of Immunology, Necker Hospital for Sick Children, AP-HP, Paris, France.ORCID 0000-0002-9902-9027
Mathieu FusaroImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0002-5332-3626
Yi WangLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-1985-3404
Xiao-Fei KongSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.ORCID 0000-0001-9983-2373
Aurélie CobatLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0001-7209-6257
David BoutboulDept. of Clinical Immunology, AP-HP, Saint-Louis Hospital, Paris, France.ORCID 0000-0002-5006-8279
Martin CastelleImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0001-9087-4411
Claire AguilarNecker Pasteur Center for Infectious Diseases and Tropical Medicine, Necker Hospital for Sick Children, AP-HP, Paris, France.ORCID 0000-0001-9181-2239
Olivier HermineImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0003-2574-3874
Morgane CheminantImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0002-2070-9581
Felipe SuarezImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0002-3537-9052
Alisan YildiranDept. of Pediatric Immunology and Allergy, Ondokuz Mayis University Medical School, Samsun, Turkey.ORCID 0000-0002-2918-6238
Aziz BousfihaClinical Immunology, Inflammation and Auto-immunity Laboratory, Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Casablanca, Morocco.ORCID 0000-0002-5011-9873
Hamoud Al-MousaTranslational Genomics, Centre for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID 0000-0003-2508-0062
Fahad AlsohimePediatric Intensive Care Unit, Dept. of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia.ORCID 0000-0002-4979-3895
Deniz CagdasSection of Pediatric Immunology, Hacettepe University, Ihsan Dogramaci Children's Hospital, Ankara, Turkey.ORCID 0000-0003-2213-4627
Roshini S AbrahamDept. of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH.ORCID 0000-0001-8109-8502
Alan P KnutsenPediatric Allergy and Immunology, Cardinal Glennon Children's Hospital, St. Louis, MO.ORCID 0000-0002-4113-2961
Borre FevangSection of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.ORCID 0000-0001-6828-0609
Sagar BhattadDept. of Pediatrics, Aster CMI Hospital, Bangalore, India.ORCID 0000-0002-5048-9727
Ayca KiykimIstanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Pediatric Immunology and Allergy, Istanbul, Turkey.ORCID 0000-0001-5821-3963
Baran ErmanInstitute of Child Health, Hacettepe University, Ankara, Turkey.ORCID 0000-0001-9398-8465
Tugba ArikogluDept. of Pediatrics, Division of Pediatric Allergy and Immunology, Mersin University Faculty of Medicine, Mersin, Turkey.ORCID 0000-0003-3340-571X
Ekrem UnalDivision of Pediatric Hematology Oncology, Dept. of Pediatrics, Erciyes University Faculty of Medicine, Kayseri, Turkey.ORCID 0000-0002-2691-4826
Ashish KumarDivision of Bone Marrow Transplantation and Immune Deficiency, Dept. of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.ORCID 0000-0002-8306-8419
Christoph B GeierDept. of Rheumatology and CCI for Chronic Immunodeficiency, Division of Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID 0000-0003-4353-8663
Ulrich BaumannDept. of Paediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.ORCID 0000-0002-0162-0266
Bénédicte NevenImagine Institute, University of Paris-Cité, Paris, France.ORCID 0000-0001-8941-0935
CARMIL2 Consortium
Meino RohlfsDept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0002-2251-2387
Christoph WalzInstitute of Pathology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.ORCID 0000-0002-6184-3592
Laurent AbelLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0001-7016-6493
Bernard MalissenCentre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, INSERM, CNRS, Marseille, France.ORCID 0000-0003-1340-9342
Nico MarrResearch Branch, Sidra Medicine, Doha, Qatar.ORCID 0000-0002-1927-7072
Christoph KleinDept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0003-0956-0445
Jean-Laurent CasanovaLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-7782-4169
Fabian Hauck *Dept. of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.ORCID 0000-0001-9644-2003
Vivien Béziat *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.ORCID 0000-0002-4020-824X
Inserm · FRLudwig-Maximilians-Universität München · DEUniversité Paris Cité · FRAssistance Publique – Hôpitaux de Paris · FRMcGill University · CANottingham University Hospitals NHS Trust · GBRockefeller University · USUniversity of Freiburg · DEDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology · RUMarmara University · TRMedizinische Hochschule Hannover · DENationwide Children's Hospital · USOslo University Hospital · NOQatar Airways (Qatar) · QAUniversity Hospital Leipzig · DEBen-Gurion University of the Negev · ILCardinal Glennon Children’s Medical Center · USCentre National de la Recherche Scientifique · FRCincinnati Children's Hospital Medical Center · USDrottning Silvias barn- och ungdomssjukhus · SE
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MMonogenic basis of resistance to SARS-CoV2 and predisposition to severe COVID-19R01AI088364 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova, Shen-Ying Zhang · 2010 to 2026
$8.7MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MInborn errors of immunity in patients with life-threatening COVID-19R01AI163029 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT, ZHANG, QIAN · 2021 to 2025
$3.7MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890kA genetic and immunological investigation of JAK-STAT in the pathogenesis of Celiac DiseaseK08DK128631 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI KONG, XIAO-FEI · 2021 to 2025
$827kHoward Hughes Medical InstituteMedical Research Council MR/W01677X/1NCATS NIH HHS UL1 TR001866NHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006504NIAID NIH HHS R01 AI088364NIAID NIH HHS R01 AI163029NIDDK NIH HHS K08 DK128631NIH HHS S10 OD018521Wellcome Trust 207556/Z/17/Z
Abstract
Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
Indexed as
CD28 AntigensMicrofilament ProteinsCD4-Positive T-LymphocytesHumansMutationPhenotypeCD28 AntigensMicrofilament Proteins
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