{"entity": "publication", "iuid": "403f0278d1874812a808b7d862806276", "timestamp": "2026-09-25T23:04:38.189Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/403f0278d1874812a808b7d862806276.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/403f0278d1874812a808b7d862806276"}}, "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-affiliated.scilifelab.se/researcher/d6bb721a88454fdab61a383d7953ef43.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-affiliated.scilifelab.se/researcher/9eccfef230a0494d87395d92b9618fb5.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-affiliated.scilifelab.se/researcher/76616d9afaaf46f9bdbc9e3b81dde4dc.json"}}, {"family": "Frosk", "given": "Patrick", "initials": "P"}, {"family": "Ma", "given": "Cindy S", "initials": "CS", "orcid": "0000-0001-5387-8413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3228c36af6cd409c8b764481adfd1e44.json"}}, {"family": "Landegren", "given": "Nils", "initials": "N"}, {"family": "Celmeli", "given": "Fatih", "initials": "F", "orcid": "0000-0002-2983-5058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7598242b190145a88fd6d5b1a6f5d132.json"}}, {"family": "Casanova", "given": "Jean-Laurent", "initials": "JL", "orcid": "0000-0002-7782-4169", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/264335517ad94440b23a027fe66f767d.json"}}, {"family": "Tangye", "given": "Stuart G", "initials": "SG"}, {"family": "Puel", "given": "Anne", "initials": "A", "orcid": "0000-0003-2603-0323", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d106604b8ad84e67870302b906a94963.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": [], "xrefs": [{"db": "pmc", "key": "PMC11406260"}], "notes": [], "created": "2026-09-23T11:24:48.338Z", "modified": "2026-09-23T11:24:48.390Z"}