{"entity": "researcher", "timestamp": "2026-04-11T07:52:04.604Z", "family": "Celmeli", "given": "Fatih", "initials": "F", "orcid": "0000-0002-2983-5058", "affiliations": ["Department of Allergy and Immunology, University of Medical Science, Antalya Education and Research Hospital, Antalya, Turkey."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/d10a5e911d694b9690bab499e0bbef99.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/d10a5e911d694b9690bab499e0bbef99"}}, "publications": [{"entity": "publication", "iuid": "85421d5b9d04415ba19ebdb36eeaee27", "links": {"self": {"href": "https://publications.scilifelab.se/publication/85421d5b9d04415ba19ebdb36eeaee27.json"}, "display": {"href": "https://publications.scilifelab.se/publication/85421d5b9d04415ba19ebdb36eeaee27"}}, "title": "Inherited human RelB deficiency impairs innate and adaptive immunity to infection.", "authors": [{"family": "Le Voyer", "given": "Tom", "initials": "T"}, {"family": "Maglorius Renkilaraj", "given": "Majistor Raj Luxman", "initials": "MRL"}, {"family": "Moriya", "given": "Kunihiko", "initials": "K"}, {"family": "P\u00e9rez Lorenzo", "given": "Malena", "initials": "M"}, {"family": "Nguyen", "given": "Tina", "initials": "T"}, {"family": "Gao", "given": "Liwei", "initials": "L"}, {"family": "Rubin", "given": "Tamar", "initials": "T"}, {"family": "Cederholm", "given": "Axel", "initials": "A"}, {"family": "Ogishi", "given": "Masato", "initials": "M", "orcid": "0000-0003-2421-7389", "researcher": {"href": "https://publications.scilifelab.se/researcher/d9205246af72422f993f696135d03d00.json"}}, {"family": "Arango-Franco", "given": "Carlos A", "initials": "CA"}, {"family": "B\u00e9ziat", "given": "Vivien", "initials": "V", "orcid": "0000-0002-4020-824X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb59e3ecbbba41c98215a9424f82d70f.json"}}, {"family": "L\u00e9vy", "given": "Romain", "initials": "R"}, {"family": "Migaud", "given": "M\u00e9lanie", "initials": "M"}, {"family": "Rapaport", "given": "Franck", "initials": "F"}, {"family": "Itan", "given": "Yuval", "initials": "Y"}, {"family": "Deenick", "given": "Elissa K", "initials": "EK"}, {"family": "Cortese", "given": "Irene", "initials": "I"}, {"family": "Lisco", "given": "Andrea", "initials": "A"}, {"family": "Boztug", "given": "Kaan", "initials": "K"}, {"family": "Abel", "given": "Laurent", "initials": "L"}, {"family": "Boisson-Dupuis", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Boisson", "given": "Bertrand", "initials": "B", "orcid": "0000-0001-5240-3555", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c47acbcc3346bcb65102b534b25cc8.json"}}, {"family": "Frosk", "given": "Patrick", "initials": "P"}, {"family": "Ma", "given": "Cindy S", "initials": "CS", "orcid": "0000-0001-5387-8413", "researcher": {"href": "https://publications.scilifelab.se/researcher/398f17ef657242a1a091b04d05388cf9.json"}}, {"family": "Landegren", "given": "Nils", "initials": "N"}, {"family": "Celmeli", "given": "Fatih", "initials": "F", "orcid": "0000-0002-2983-5058", "researcher": {"href": "https://publications.scilifelab.se/researcher/d10a5e911d694b9690bab499e0bbef99.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL", "orcid": "0000-0002-7782-4169", "researcher": {"href": "https://publications.scilifelab.se/researcher/009e2306468648c08fb1eea319f0c488.json"}}, {"family": "Tangye", "given": "Stuart G", "initials": "SG"}, {"family": "Puel", "given": "Anne", "initials": "A", "orcid": "0000-0003-2603-0323", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bcef4c205904e5db9e36f3aadaa13bb.json"}}], "type": "journal article", "published": "2024-09-10", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "121", "issue": "37", "pages": "e2321794121", "issn-l": "0027-8424"}, "abstract": "We report two unrelated adults with homozygous (P1) or compound heterozygous (P2) private loss-of-function variants of V-Rel Reticuloendotheliosis Viral Oncogene Homolog B (RELB). The resulting deficiency of functional RelB impairs the induction of NFKB2 mRNA and NF-\u03baB2 (p100/p52) protein by lymphotoxin in the fibroblasts of the patients. These defects are rescued by transduction with wild-type RELB complementary DNA (cDNA). By contrast, the response of RelB-deficient fibroblasts to Tumor Necrosis Factor (TNF) or IL-1\u03b2 via the canonical NF-\u03baB pathway remains intact. P1 and P2 have low proportions of na\u00efve CD4+ and CD8+ T cells and of memory B cells. Moreover, their na\u00efve B cells cannot differentiate into immunoglobulin G (IgG)- or immunoglobulin A (IgA)-secreting cells in response to CD40L/IL-21, and the development of IL-17A/F-producing T cells is strongly impaired in vitro. Finally, the patients produce neutralizing autoantibodies against type I interferons (IFNs), even after hematopoietic stem cell transplantation, attesting to a persistent dysfunction of thymic epithelial cells in T cell selection and central tolerance to some autoantigens. Thus, inherited human RelB deficiency disrupts the alternative NF-\u03baB pathway, underlying a T- and B cell immunodeficiency, which, together with neutralizing autoantibodies against type I IFNs, confers a predisposition to viral, bacterial, and fungal infections.", "doi": "10.1073/pnas.2321794121", "pmid": "39231201", "labels": {"Autoimmunity and Serology Profiling": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11406260"}], "notes": [], "created": "2024-09-23T11:59:51.904Z", "modified": "2024-09-23T11:59:52.726Z"}, {"entity": "publication", "iuid": "80543734f42047bd8b359d3a2c96c420", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80543734f42047bd8b359d3a2c96c420.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80543734f42047bd8b359d3a2c96c420"}}, "title": "Autoantibodies against type I IFNs in humans with alternative NF-\u03baB pathway deficiency.", "authors": [{"family": "Le Voyer", "given": "Tom", "initials": "T", "orcid": 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"B"}, {"family": "Fieschi", "given": "Claire", "initials": "C"}, {"family": "Berteloot", "given": "Laureline", "initials": "L", "orcid": "0000-0001-9681-3142", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa0ce699420749dc97617accb080b2e8.json"}}, {"family": "Bryant", "given": "Vanessa L", "initials": "VL"}, {"family": "Trouillet Assant", "given": "Sophie", "initials": "S"}, {"family": "Su", "given": "Helen", "initials": "H", "orcid": "0000-0002-5582-9110", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f3b00f2707541b39b2205d70fd2d6f7.json"}}, {"family": "Neven", "given": "Benedicte", "initials": "B"}, {"family": "Abel", "given": "Laurent", "initials": "L"}, {"family": "Zhang", "given": "Qian", "initials": "Q"}, {"family": "Boisson", "given": "Bertrand", "initials": "B", "orcid": "0000-0001-5240-3555", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7c47acbcc3346bcb65102b534b25cc8.json"}}, {"family": "Cobat", "given": "Aur\u00e9lie", "initials": "A", "orcid": "0000-0001-7209-6257", "researcher": {"href": "https://publications.scilifelab.se/researcher/eaba2f9452294eec89161b589d96ff29.json"}}, {"family": "Jouanguy", "given": "Emmanuelle", "initials": "E"}, {"family": "Kampe", "given": "Olle", "initials": "O", "orcid": "0000-0001-6091-9914", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c547dc809a14cdaa47b623cf638162b.json"}}, {"family": "Bastard", "given": "Paul", "initials": "P"}, {"family": "Roifman", "given": "Chaim M", "initials": "CM"}, {"family": "Landegren", "given": "Nils", "initials": "N"}, {"family": "Notarangelo", "given": "Luigi D", "initials": "LD", "orcid": "0000-0002-8335-0262", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8d346e44c2d443ba3da3fcf2725b96c.json"}}, {"family": "Anderson", "given": "Mark S", "initials": "MS", "orcid": "0000-0002-3093-4758", "researcher": {"href": "https://publications.scilifelab.se/researcher/4276efc31c1d4dbaaa242f11ef60c51e.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL", "orcid": "0000-0002-7782-4169", "researcher": {"href": "https://publications.scilifelab.se/researcher/009e2306468648c08fb1eea319f0c488.json"}}, {"family": "Puel", "given": "Anne", "initials": "A", "orcid": "0000-0003-2603-0323", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bcef4c205904e5db9e36f3aadaa13bb.json"}}], "type": "journal article", "published": "2023-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "623", "issue": "7988", "pages": "803-813", "issn-l": "0028-0836"}, "abstract": "Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-\u03baB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-\u03baB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (I\u03baB\u03b4 activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of I\u03baB\u03b4 (hereafter, p52LOF/I\u03baB\u03b4GOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/I\u03baB\u03b4LOF) or gain-of-function of p52 (hereafter, p52GOF/I\u03baB\u03b4LOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-\u03baB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-\u03baB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.", "doi": "10.1038/s41586-023-06717-x", "pmid": "37938781", "labels": {"Autoimmunity and Serology Profiling": "Service", "Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10665196"}, {"db": "pii", "key": "10.1038/s41586-023-06717-x"}], "notes": [], "created": "2023-11-16T13:27:25.515Z", "modified": "2024-11-28T18:23:58.185Z"}]}