Academic Journal
Clinical and immunological characterization of NFKB1 haploinsufficiency in Japan.
| Τίτλος: | Clinical and immunological characterization of NFKB1 haploinsufficiency in Japan. |
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| Συγγραφείς: | Moriya K; Department of Pediatrics, National Defense Medical College, Saitama, Japan.; Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan., Kamiyama Y; Department of Pediatrics, National Defense Medical College, Saitama, Japan.; Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Ogino R; Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan., Kaneko S; Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan., Isoda T; Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan., Kamiya T; Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan., Sakai Y; Department of Pediatrics, National Defense Medical College, Saitama, Japan., Hirose F; Department of Pediatrics, National Defense Medical College, Saitama, Japan., Hagiwara H; Department of Pediatrics, National Defense Medical College, Saitama, Japan., Iwama I; Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan., Nambu R; Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan., Uejima Y; Department of Infectious Diseases and Immunology, Division of Infectious Diseases and Immunology, Saitama Children's Medical Center, Saitama, Japan., Sakura F; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Tsumura M; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Izawa K; Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan., Matsuda Y; Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan., Nakatani N; Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan., Tamura A; Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan., Nozawa T; Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Shimizu M; Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan., Wada T; Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan., Okada S; Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan., Kanegane H; Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan., Imai K; Department of Pediatrics, National Defense Medical College, Saitama, Japan. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Jul 08; Vol. 17, pp. 1866459. Date of Electronic Publication: 2026 Jul 08 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | NF-kappa B p50 Subunit*/genetics , Agammaglobulinemia*/genetics , Agammaglobulinemia*/immunology , Common Variable Immunodeficiency*/genetics , Common Variable Immunodeficiency*/immunology , Haploinsufficiency*, B-Lymphocytes/immunology ; Humans ; Female ; Male ; Adult ; Child ; Adolescent ; Japan ; Child, Preschool ; Young Adult ; Middle Aged ; Immunophenotyping ; Pedigree ; Phenotype |
| Περίληψη: | Background: NFKB1 haploinsufficiency caused by monoallelic loss-of-function variants in NFKB1 results in a CVID-like phenotype or other forms of hypogammaglobulinemia. Objective: This study aims to characterize the clinical and immunological profiles of 21 individuals from nine families with this disorder. Methods: Gene panel sequence and/or whole exome sequence, followed by Sanger sequencing, were used to identify and confirm NFKB1 variants. Immunophenotyping were performed by flow cytometry. The type I interferon signature was determined by quantitative PCR. Results: Of the nine NFKB1 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. Conclusions: In addition to hypogammaglobulinemia/CVID-like phenotype, NFKB1 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. (Copyright © 2026 Moriya, Kamiyama, Ogino, Kaneko, Isoda, Kamiya, Sakai, Hirose, Hagiwara, Iwama, Nambu, Uejima, Sakura, Tsumura, Izawa, Matsuda, Nakatani, Tamura, Nozawa, Shimizu, Wada, Okada, Kanegane and Imai.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor BP declared a past co-authorship with the author(s) KM, KI. |
| Σχόλια: | Erratum in: Front Immunol. 2026 Aug 10;17:1933982. doi: 10.3389/fimmu.2026.1933982.. (PMID: 42639479) |
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| Contributed Indexing: | Keywords: NFKB1; autoimmunity; autoinfammatory disease; common variable immunodeficiency (CVID); inborn errors of immunity (IEI) |
| Substance Nomenclature: | 0 (NF-kappa B p50 Subunit) 0 (NFKB1 protein, human) |
| Entry Date(s): | Date Created: 20260723 Date Completed: 20260723 Latest Revision: 20260825 |
| Update Code: | 20260825 |
| PubMed Central ID: | PMC13388040 |
| DOI: | 10.3389/fimmu.2026.1866459 |
| PMID: | 42488646 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1866459 |