{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:47:06Z","timestamp":1785433626464,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,20]]},"group-title":"Allergy and Immunology","reference-count":114,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AI095983"],"award-info":[{"award-number":["R01AI095983"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  We previously reported inherited ROR\u03b3T deficiency in seven patients from three ancestries (Chilean, Palestinian, Saudi Arabian) with mycobacterial disease and chronic mucocutaneous candidiasis (CMC). We report here five additional patients from different ancestries (Afghan, Indian, Iranian, Japanese, Sri Lankan), each homozygous for a new loss-of-function\n                  <jats:italic>RORC<\/jats:italic>\n                  variant. All but one patient \u2014 the exception receiving early prophylaxis \u2014 developed mycobacterial disease due to a near-complete depletion of innate-like adaptive T cells, including MAIT and iNKT cells, low counts of adaptive T\n                  <jats:sub>H<\/jats:sub>\n                  1* and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, and impaired\n                  <jats:italic>Mycobacterium<\/jats:italic>\n                  -induced IFN-\u03b3 production by the remaining cells of these subsets, NK cells, conventional CD4\n                  <jats:sup>+<\/jats:sup>\n                  T, V\u03b41, and V\u03b42 \u03b3\u03b4T cells. Most patients also displayed CMC due to their low counts of T\n                  <jats:sub>H<\/jats:sub>\n                  17 and T\n                  <jats:sub>H<\/jats:sub>\n                  1* cells. One patient died from disseminated Bacille Calmette-Gu\u00e9rin (BCG) vaccine infection, but, unexpectedly, all the other patients are still alive and clinically stable. ROR\u03b3T is essential for protective immunity against mycobacteria and\n                  <jats:italic>Candida<\/jats:italic>\n                  in humans.\n                <\/jats:p>","DOI":"10.64898\/2026.07.18.26358075","type":"posted-content","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:05:13Z","timestamp":1784592313000},"source":"Crossref","is-referenced-by-count":0,"title":["Human inherited ROR\u03b3T deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity"],"prefix":"10.64898","author":[{"given":"Iris","family":"Fagniez","sequence":"first","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Tsumura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Guerin","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Sydney, Australia"},{"name":"School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Abolhassani","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden"},{"name":"Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Childre\u0144s Medical Center, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samin","family":"Sharafian","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Mofid Children\u2019s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrnaz","family":"Mesdaghi","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Mofid Children\u2019s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyoki","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki City, Miyazaki, 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsha Prasada","family":"Lashkari","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576 104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadashiva","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 576 104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Richards","sequence":"additional","affiliation":[{"name":"Royal Children\u2019s Hospital, Allergy & Immunology, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Han","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia M.","family":"Delmonte","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Kergaravat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut de Recherche Saint Louis, INSERM UMR 1342; Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet G.","family":"Markle","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"},{"name":"Department of Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Ogishi","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Peel","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Vellutini","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Feng","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Soud\u00e9e","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France"},{"name":"Paris Cit\u00e9 University, Imagine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Migaud","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France"},{"name":"Paris Cit\u00e9 University, Imagine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boaz","family":"Palterer","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J L","family":"Jackson","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Sakata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishiro","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki City, Miyazaki, 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Moritake","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki City, Miyazaki, 889-1692, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Security Forces Hospital, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Vallejos","sequence":"additional","affiliation":[{"name":"Division of Pediatric Immunology, Gustavo Fricke Hospital, Valparaiso, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa L","family":"Cole","sequence":"additional","affiliation":[{"name":"Royal Children\u2019s Hospital, Allergy & Immunology, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M","family":"Smart","sequence":"additional","affiliation":[{"name":"Royal Children\u2019s Hospital, Allergy & Immunology, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Choo","sequence":"additional","affiliation":[{"name":"Royal Children\u2019s Hospital, Allergy & Immunology, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Chavoshzadeh","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Mofid Children\u2019s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahnaz","family":"Armin","sequence":"additional","affiliation":[{"name":"Pediatric Infections Research Center, Research Institute for Children\u2019s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Toubert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Institut de Recherche Saint Louis, INSERM UMR 1342; Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France"},{"name":"Paris Cit\u00e9 University, Imagine Institute, 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Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072202301149000_2026.07.18.26358075v1.1","doi-asserted-by":"crossref","unstructured":"Abramson, J. , J. Dobe\u0161 , M. Lyu , and G.F. Sonnenberg . 2023. The emerging family of ROR\u03b3t(+) antigen-presenting cells. 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