{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:52:13Z","timestamp":1782237133804,"version":"3.54.5"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2024-I2M-C&T-B-014"],"award-info":[{"award-number":["2024-I2M-C&T-B-014"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2025-PUMCH-D-006"],"award-info":[{"award-number":["2025-PUMCH-D-006"]}]},{"name":"Open Research Fund of the State Key Laboratory of Complex, Severe, and Rare Diseases","award":["2025-O-ZD-005"],"award-info":[{"award-number":["2025-O-ZD-005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The nuclear factor \u03baB (NF-\u03baB)-related disorders encompassed not only common variable immunodeficiency but also manifestations of autoinflammation, autoimmunity, and malignancies. While most cases have been reported in European populations, reports in the Chinese population are sparse. Clinical data and genetic variants from four Chinese patients with NFKB1 variants, alongside four previously reported cases, were analyzed and compared with an international cohort. Additionally, comprehensive in vitro functional assays\u2014including immunoblotting, transcript analyses, dual-luciferase reporter, and co-immunoprecipitation assays\u2014were conducted to explore the molecular defects of the novel variants. Our cohort included three men and one woman, all presenting with recurrent fever and hypogammaglobulinemia. Three patients experienced recurrent sinopulmonary infections, accompanied by decreased B cells and NK cells, while two patients developed pneumonia, bronchiectasis, and hepatitis. Three novel NFKB1 (NM_003998) variants were identified: c.559C &amp;gt; T (p. Arg187Trp), c.1509del (p. Glu504Argfs*19), and c.1753-11_1760del (p. Thr585Alafs*9). Functional analyses revealed distinct pathomechanisms: the frameshift\/splicing variants drive classical haploinsufficiency via nonsense-mediated mRNA decay (NMD), triggering compensatory inflammatory hyperactivation; conversely, the p.Arg187Trp missense variant maintains protein stability and heterodimerization but strictly abolishes DNA-binding capacity. Compared to a previously reported cohort, Chinese patients were predominantly male, had a later median age of onset and diagnosis. Notably, Chinese patients exhibited a higher prevalence of hepatitis (25%) and cirrhosis (12.5%), potentially reflecting the high endemicity of hepatitis B virus in China. They also showed increased rates of viral infections, sepsis, and bronchiectasis, with more pronounced reductions in NK and B cells. In contrast, autoimmune diseases and bronchitis were less frequent than in the foreign cohort. This study represents the first and largest case series of Chinese patients with NF-\u03baB1-related diseases, providing molecular characterization for three novel variants. In this limited case series, the observed delayed onset and frequent hepatic complications in our cohort may reflect regional factors, such as HBV endemicity, or ascertainment bias. Our findings underscore that suspected AOSD accompanied by hypogammaglobulinemia warrants immediate genetic investigation. Early diagnosis is essential to prioritize immunoglobulin replacement and prevent fatal complications from immunosuppressive therapy.<\/jats:p>","DOI":"10.1093\/cei\/uxag033","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:46:09Z","timestamp":1780659969000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical, genetic, and functional characterization of novel\n                    <i>NFKB1<\/i>\n                    variants in Chinese patients with primary immunodeficiency"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3524-2590","authenticated-orcid":false,"given":"Jingyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100730 ,","place":["China"]},{"name":"State Key Laboratory of Complex Severe and Rare Diseases , PUMCH, Beijing 100730 ,","place":["China"]},{"name":"Department of Rheumatology and Clinical Immunology , PUMCH, Beijing 100730 ,","place":["China"]},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology , Beijing 100730 ,","place":["China"]},{"name":"Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huacong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tienan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100730 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-126X","authenticated-orcid":false,"given":"Min","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100730 ,","place":["China"]},{"name":"State Key Laboratory of Complex Severe and Rare Diseases, PUMCH , Beijing 100730 ,","place":["China"]},{"name":"Department of Rheumatology and Clinical Immunology, PUMCH , Beijing 100730 ,","place":["China"]},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology , Beijing 100730 ,","place":["China"]},{"name":"Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing 100730 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