{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:01:47Z","timestamp":1791842507838,"version":"4.3.4"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1007\/s10875-024-01843-1","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T02:35:25Z","timestamp":1732329325000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs"],"prefix":"10.1007","volume":"45","author":[{"given":"Alperen","family":"Baran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysima","family":"At\u0131lgan L\u00fclecio\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y\u0131lmaz Y\u00fccehan","family":"Yaz\u0131c\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fevzi","family":"Demirel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Metin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Laurent","family":"Casanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Puel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Le","family":"Voyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eeng\u00fcl","family":"Beyaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Belkaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"issue":"9","key":"1843_CR1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1136\/jmedgenet-2015-103690","volume":"53","author":"DJ Bogaert","year":"2016","unstructured":"Bogaert DJ, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F. Genes associated with common variable immunodeficiency: one diagnosis to rule them all? J Med Genet. 2016;53(9):575\u201390.","journal-title":"J Med Genet"},{"issue":"5","key":"1843_CR2","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.anai.2019.07.014","volume":"123","author":"S Agarwal","year":"2019","unstructured":"Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Ann Allergy Asthma Immunol. 2019;123(5):454\u201360.","journal-title":"Ann Allergy Asthma Immunol"},{"issue":"1","key":"1843_CR3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.18176\/jiaci.0388","volume":"30","author":"R Yazdani","year":"2020","unstructured":"Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, et al. Common variable immunodeficiency: Epidemiology, Pathogenesis, clinical manifestations, diagnosis, classification, and management. J Investig Allergol Clin Immunol. 2020;30(1):14\u201334.","journal-title":"J Investig Allergol Clin Immunol"},{"issue":"1","key":"1843_CR4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","volume":"4","author":"FA Bonilla","year":"2016","unstructured":"Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): Common Variable Immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38\u201359.","journal-title":"J Allergy Clin Immunol Pract"},{"key":"1843_CR5","doi-asserted-by":"publisher","first-page":"1272912","DOI":"10.3389\/fgene.2023.1272912","volume":"14","author":"C Cunningham-Rundles","year":"2023","unstructured":"Cunningham-Rundles C, Casanova JL, Boisson B. Genetics and clinical phenotypes in common variable immunodeficiency. Front Genet. 2023;14:1272912.","journal-title":"Front Genet"},{"key":"1843_CR6","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1146\/annurev-pathmechdis-031521-024229","volume":"18","author":"XP Peng","year":"2023","unstructured":"Peng XP, Caballero-Oteyza A, Grimbacher B. Common variable immunodeficiency: more pathways than roads to Rome. Annu Rev Pathol. 2023;18:283\u2013310.","journal-title":"Annu Rev Pathol"},{"issue":"1","key":"1843_CR7","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/s41436-018-0012-x","volume":"21","author":"H Abolhassani","year":"2019","unstructured":"Abolhassani H, Aghamohammadi A, Fang M, Rezaei N, Jiang C, Liu X, et al. Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency. Genet Med. 2019;21(1):243\u201351.","journal-title":"Genet Med"},{"issue":"3","key":"1843_CR8","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/cei.12947","volume":"188","author":"AK Kienzler","year":"2017","unstructured":"Kienzler AK, Hargreaves CE, Patel SY. The role of genomics in common variable immunodeficiency disorders. Clin Exp Immunol. 2017;188(3):326\u201332.","journal-title":"Clin Exp Immunol"},{"key":"1843_CR9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3389\/fimmu.2019.00297","volume":"10","author":"C Klemann","year":"2019","unstructured":"Klemann C, Camacho-Ordonez N, Yang L, Eskandarian Z, Rojas-Restrepo JL, Frede N, et al. Clinical and immunological phenotype of patients with primary Immunodeficiency due to damaging mutations in NFKB2. Front Immunol. 2019;10:297.","journal-title":"Front Immunol"},{"issue":"9","key":"1843_CR10","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nri.2017.52","volume":"17","author":"SC Sun","year":"2017","unstructured":"Sun SC. The non-canonical NF-kappaB pathway in immunity and inflammation. Nat Rev Immunol. 2017;17(9):545\u201358.","journal-title":"Nat Rev Immunol"},{"issue":"7988","key":"1843_CR11","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/s41586-023-06717-x","volume":"623","author":"T Le Voyer","year":"2023","unstructured":"Le Voyer T, Parent AV, Liu X, Cederholm A, Gervais A, Rosain J, et al. Autoantibodies against type I IFNs in humans with alternative NF-kappaB pathway deficiency. Nature. 2023;623(7988):803\u201313.","journal-title":"Nature"},{"issue":"5","key":"1843_CR12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/s41590-024-01815-y","volume":"25","author":"JL Casanova","year":"2024","unstructured":"Casanova JL, Peel J, Donadieu J, Neehus AL, Puel A, Bastard P. The ouroboros of autoimmunity. Nat Immunol. 2024;25(5):743\u201354.","journal-title":"Nat Immunol"},{"issue":"8","key":"1843_CR13","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1084\/jem.20190669","volume":"216","author":"S Belkaya","year":"2019","unstructured":"Belkaya S, Michailidis E, Korol CB, Kabbani M, Cobat A, Bastard P, et al. Inherited IL-18BP deficiency in human fulminant viral hepatitis. J Exp Med. 2019;216(8):1777\u201390.","journal-title":"J Exp Med"},{"issue":"6","key":"1843_CR14","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.4049\/jimmunol.158.6.2576","volume":"158","author":"A Durandy","year":"1997","unstructured":"Durandy A, Hivroz C, Mazerolles F, Schiff C, Bernard F, Jouanguy E, et al. Abnormal CD40-mediated activation pathway in B lymphocytes from patients with hyper-IgM syndrome and normal CD40 ligand expression. J Immunol. 1997;158(6):2576\u201384.","journal-title":"J Immunol"},{"issue":"1","key":"1843_CR15","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s10875-022-01369-4","volume":"43","author":"ZG Tepe","year":"2023","unstructured":"Tepe ZG, Yazici YY, Tank U, Kose LI, Ozer M, Aytekin C, et al. Inherited IRAK-4 Deficiency in Acute Human Herpesvirus-6 Encephalitis. J Clin Immunol. 2023;43(1):192\u2013205.","journal-title":"J Clin Immunol"},{"issue":"7809","key":"1843_CR16","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581(7809):434\u201343.","journal-title":"Nature"},{"issue":"7845","key":"1843_CR17","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","volume":"590","author":"D Taliun","year":"2021","unstructured":"Taliun D, Harris DN, Kessler MD, Carlson J, Szpiech ZA, Torres R, et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program. Nature. 2021;590(7845):290\u20139.","journal-title":"Nature"},{"key":"1843_CR18","doi-asserted-by":"crossref","unstructured":"Li S, Carss KJ, Halldorsson BV, Cortes A. Whole-genome sequencing of half-a-million UK Biobank participants. medRxiv. 2023;2023.12.06.23299426.","DOI":"10.1101\/2023.12.06.23299426"},{"issue":"6664","key":"1843_CR19","doi-asserted-by":"publisher","first-page":"eadg7492","DOI":"10.1126\/science.adg7492","volume":"381","author":"J Cheng","year":"2023","unstructured":"Cheng J, Novati G, Pan J, Bycroft C, Zemgulyte A, Applebaum T, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023;381(6664):eadg7492.","journal-title":"Science"},{"key":"1843_CR20","doi-asserted-by":"crossref","unstructured":"Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248\u20139.","DOI":"10.1038\/nmeth0410-248"},{"key":"1843_CR21","doi-asserted-by":"crossref","unstructured":"Steinhaus R, Proft S, Schuelke M, Cooper DN, Schwarz JM, Seelow D. MutationTaster2021. Nucleic Acids Res. 2021;49(W1):W446-W51.","DOI":"10.1093\/nar\/gkab266"},{"issue":"1","key":"1843_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nprot.2015.123","volume":"11","author":"R Vaser","year":"2016","unstructured":"Vaser R, Adusumalli S, Leng SN, Sikic M, Ng PC. SIFT missense predictions for genomes. Nat Protoc. 2016;11(1):1\u20139.","journal-title":"Nat Protoc"},{"issue":"5","key":"1843_CR23","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"1","key":"1843_CR24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jaci.2013.12.1077","volume":"134","author":"B Gathmann","year":"2014","unstructured":"Gathmann B, Mahlaoui N, Ceredih, Gerard L, Oksenhendler E, Warnatz K, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(1):116\u201326.","journal-title":"J Allergy Clin Immunol"},{"key":"1843_CR25","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.3389\/fimmu.2017.01190","volume":"8","author":"JS Selenius","year":"2017","unstructured":"Selenius JS, Martelius T, Pikkarainen S, Siitonen S, Mattila E, Pietikainen R, et al. Unexpectedly high prevalence of common variable immunodeficiency in Finland. Front Immunol. 2017;8:1190.","journal-title":"Front Immunol"},{"key":"1843_CR26","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3389\/fimmu.2016.00220","volume":"7","author":"P Maffucci","year":"2016","unstructured":"Maffucci P, Filion CA, Boisson B, Itan Y, Shang L, Casanova JL, et al. Genetic diagnosis using whole Exome sequencing in common variable immunodeficiency. Front Immunol. 2016;7:220.","journal-title":"Front Immunol"},{"issue":"7","key":"1843_CR27","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1007\/s10875-022-01352-z","volume":"42","author":"A Bousfiha","year":"2022","unstructured":"Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 update of IUIS Phenotypical classification for human inborn errors of immunity. J Clin Immunol. 2022;42(7):1508\u201320.","journal-title":"J Clin Immunol"},{"key":"1843_CR28","unstructured":"Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J et al. Autoantibodies neutralizing type I IFNs are present in ~\u20094% of uninfected individuals over 70 years old and account for ~\u200920% of COVID-19 deaths. Sci Immunol. 2021;6(62)."},{"issue":"3","key":"1843_CR29","doi-asserted-by":"publisher","first-page":"e13116","DOI":"10.1111\/irv.13116","volume":"17","author":"F Alotaibi","year":"2023","unstructured":"Alotaibi F, Alharbi NK, Rosen LB, Asiri AY, Assiri AM, Balkhy HH, et al. Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial. Influenza Other Respir Viruses. 2023;17(3):e13116.","journal-title":"Influenza Other Respir Viruses"},{"key":"1843_CR30","doi-asserted-by":"crossref","unstructured":"Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T, Rosain J et al. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J Exp Med. 2021;218(4).","DOI":"10.1084\/jem.20202486"},{"key":"1843_CR31","unstructured":"Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515)."},{"key":"1843_CR32","unstructured":"Gervais A, Rovida F, Avanzini MA, Croce S, Marchal A, Lin SC et al. Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in approximately 40% of patients. J Exp Med. 2023;220(9)."},{"key":"1843_CR33","doi-asserted-by":"publisher","first-page":"108851","DOI":"10.1016\/j.clim.2021.108851","volume":"231","author":"I Hetemaki","year":"2021","unstructured":"Hetemaki I, Laakso S, Valimaa H, Kleino I, Kekalainen E, Makitie O, et al. Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections. Clin Immunol. 2021;231:108851.","journal-title":"Clin Immunol"},{"issue":"21","key":"1843_CR34","doi-asserted-by":"publisher","first-page":"e2200413119","DOI":"10.1073\/pnas.2200413119","volume":"119","author":"J Manry","year":"2022","unstructured":"Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, et al. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proc Natl Acad Sci U S A. 2022;119(21):e2200413119.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"1843_CR35","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1136\/ard-2022-222549","volume":"81","author":"A Mathian","year":"2022","unstructured":"Mathian A, Breillat P, Dorgham K, Bastard P, Charre C, Lhote R, et al. Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-alpha. Ann Rheum Dis. 2022;81(12):1695\u2013703.","journal-title":"Ann Rheum Dis"},{"key":"1843_CR36","doi-asserted-by":"crossref","unstructured":"Meisel C, Akbil B, Meyer T, Lankes E, Corman VM, Staudacher O et al. Mild COVID-19 despite autoantibodies against type I IFNs in autoimmune polyendocrine syndrome type 1. J Clin Invest. 2021;131(14).","DOI":"10.1172\/JCI150867"},{"issue":"5","key":"1843_CR37","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1093\/infdis\/150.5.707","volume":"150","author":"B Pozzetto","year":"1984","unstructured":"Pozzetto B, Mogensen KE, Tovey MG, Gresser I. Characteristics of autoantibodies to human interferon in a patient with varicella-zoster disease. J Infect Dis. 1984;150(5):707\u201313.","journal-title":"J Infect Dis"},{"issue":"7902","key":"1843_CR38","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41586-022-04447-0","volume":"603","author":"Q Zhang","year":"2022","unstructured":"Zhang Q, Bastard P, Effort CHG, Cobat A, Casanova JL. Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature. 2022;603(7902):587\u201398.","journal-title":"Nature"},{"key":"1843_CR39","unstructured":"Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T et al. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J Exp Med. 2022;219(11)."},{"key":"1843_CR40","doi-asserted-by":"crossref","unstructured":"Schubach M, Maass T, Nazaretyan L, R\u00f6ner S, Kircher M. CADD v1.7: using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions. Nucleic Acids Res. 2024;52(D1):D1143\u2013D1154.","DOI":"10.1093\/nar\/gkad989"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01843-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-024-01843-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01843-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T15:45:31Z","timestamp":1777304731000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-024-01843-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,23]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["1843"],"URL":"https:\/\/doi.org\/10.1007\/s10875-024-01843-1","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"value":"0271-9142","type":"print"},{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,23]]},"assertion":[{"value":"16 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the institutional, local, and national ethical guidelines, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the \u0130hsan Do\u011framac\u0131 Bilkent University Ethics Committee (#2022_04_28_01).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Written informed consent was obtained from all individual participants included in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"48"}}