{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:31:07Z","timestamp":1786375867255,"version":"build-2736575974"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>NFKB1<\/jats:italic>\n                      haploinsufficiency caused by monoallelic loss-of-function variants in\n                      <jats:italic>NFKB1<\/jats:italic>\n                      results in a CVID-like phenotype or other forms of hypogammaglobulinemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to characterize the clinical and immunological profiles of 21 individuals from nine families with this disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Gene panel sequence and\/or whole exome sequence, followed by Sanger sequencing, were used to identify and confirm\n                      <jats:italic>NFKB1<\/jats:italic>\n                      variants. Immunophenotyping were performed by flow cytometry. The type I interferon signature was determined by quantitative PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the nine\n                      <jats:italic>NFKB1<\/jats:italic>\n                      variants, seven novel heterozygous variants were identified in this study. Ten individuals were clinically asymptomatic, while 11 were symptomatic, resulting in clinical penetrance of 52%. However, immunologic abnormalities were observed in all asymptomatic family members tested (n=9). The main presenting symptoms in symptomatic individuals were respiratory tract infections (7\/11) and autoimmune or autoinflammatory features (7\/11). Interestingly, two patients had Moyamoya disease, and one patient was complicated by alopecia and rheumatoid arthritis. Immunological analyses were performed in 19 individuals, including 9 asymptomatic, and revealed that 58% had low absolute T cell counts and that 72% of individuals displayed inverted CD4\/CD8 T-cell ratio. B-cell lymphopenia and decreased switch memory B cells were observed in 42% and 61% of individuals, respectively. A type I interferon signature was not observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In addition to hypogammaglobulinemia\/CVID-like phenotype,\n                      <jats:italic>NFKB1<\/jats:italic>\n                      variants have been associated with a wide range of manifestations, ranging from various organ involvements to autoimmunity. Autoinflammatory features have also been reported; however, the presence of type I interferon signatures was not specifically addressed in this study.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1866459","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:46:29Z","timestamp":1783485989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and immunological characterization of NFKB1 haploinsufficiency in Japan"],"prefix":"10.3389","volume":"17","author":[{"given":"Kunihiko","family":"Moriya","sequence":"first","affiliation":[{"name":"Department of Pediatrics, National Defense Medical College","place":["Saitama, Japan"]},{"name":"Department of Antibody Drug Development, Tohoku University Graduate School of Medicine","place":["Sendai, 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