NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications
dc.contributor.author | Bodansky, Aaron | |
dc.contributor.author | Vazquez, Sara E. | |
dc.contributor.author | Chou, Janet | |
dc.contributor.author | Novak, Tanya | |
dc.contributor.author | Al-Musa, Amer | |
dc.contributor.author | Young, Cameron | |
dc.contributor.author | Newhams, Margaret | |
dc.contributor.author | Kucukak, Suden | |
dc.contributor.author | Zambrano, Laura D. | |
dc.contributor.author | Mitchell, Anthea | |
dc.contributor.author | Wang, Chung-Yu | |
dc.contributor.author | Moffitt, Kristin | |
dc.contributor.author | Halasa, Natasha B. | |
dc.contributor.author | Loftis, Laura L. | |
dc.contributor.author | Schwartz, Stephanie P. | |
dc.contributor.author | Walker, Tracie C. | |
dc.contributor.author | Mack, Elizabeth H. | |
dc.contributor.author | Fitzgerald, Julie C. | |
dc.contributor.author | Gertz, Shira J. | |
dc.contributor.author | Rowan, Courtney M. | |
dc.contributor.author | Irby, Katherine | |
dc.contributor.author | Sanders, Ronald C., Jr. | |
dc.contributor.author | Kong, Michele | |
dc.contributor.author | Schuster, Jennifer E. | |
dc.contributor.author | Staat, Mary A. | |
dc.contributor.author | Zinter, Matt S. | |
dc.contributor.author | Cvijanovich, Natalie Z. | |
dc.contributor.author | Tarquinio, Keiko M. | |
dc.contributor.author | Coates, Bria M. | |
dc.contributor.author | Flori, Heidi R. | |
dc.contributor.author | Dahmer, Mary K. | |
dc.contributor.author | Crandall, Hillary | |
dc.contributor.author | Cullimore, Melissa L. | |
dc.contributor.author | Levy, Emily R. | |
dc.contributor.author | Chatani, Brandon | |
dc.contributor.author | Nofziger, Ryan | |
dc.contributor.author | Overcoming COVID-19 Network Study Group Investigators | |
dc.contributor.author | Geha, Raif S. | |
dc.contributor.author | DeRisi, Joseph | |
dc.contributor.author | Campbell, Angela P. | |
dc.contributor.author | Anderson, Mark | |
dc.contributor.author | Randolph, Adrienne G. | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2023-10-09T10:47:39Z | |
dc.date.available | 2023-10-09T10:47:39Z | |
dc.date.issued | 2023 | |
dc.description.abstract | Background: Autoantibodies against type I IFNs occur in approximately 10% of adults with life-threatening coronavirus disease 2019 (COVID-19). The frequency of anti-IFN autoantibodies in children with severe sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. Objective: We quantified anti-type I IFN autoantibodies in a multicenter cohort of children with severe COVID-19, multisystem inflammatory syndrome in children (MIS-C), and mild SARS-CoV-2 infections. Methods: Circulating anti-IFN-α2 antibodies were measured by a radioligand binding assay. Whole-exome sequencing, RNA sequencing, and functional studies of peripheral blood mononuclear cells were used to study any patients with levels of anti-IFN-α2 autoantibodies exceeding the assay's positive control. Results: Among 168 patients with severe COVID-19, 199 with MIS-C, and 45 with mild SARS-CoV-2 infections, only 1 had high levels of anti-IFN-α2 antibodies. Anti-IFN-α2 autoantibodies were not detected in patients treated with intravenous immunoglobulin before sample collection. Whole-exome sequencing identified a missense variant in the ankyrin domain of NFKB2, encoding the p100 subunit of nuclear factor kappa-light-chain enhancer of activated B cells, aka NF-κB, essential for noncanonical NF-κB signaling. The patient's peripheral blood mononuclear cells exhibited impaired cleavage of p100 characteristic of NFKB2 haploinsufficiency, an inborn error of immunity with a high prevalence of autoimmunity. Conclusions: High levels of anti-IFN-α2 autoantibodies in children and adolescents with MIS-C, severe COVID-19, and mild SARS-CoV-2 infections are rare but can occur in patients with inborn errors of immunity. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Bodansky A, Vazquez SE, Chou J, et al. NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications. J Allergy Clin Immunol. 2023;151(4):926-930.e2. doi:10.1016/j.jaci.2022.11.020 | |
dc.identifier.uri | https://hdl.handle.net/1805/36208 | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | |
dc.relation.isversionof | 10.1016/j.jaci.2022.11.020 | |
dc.relation.journal | Journal of Allergy and Clinical Immunology | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Anti-interferon autoantibody | |
dc.subject | COVID-19 | |
dc.subject | MIS-C | |
dc.subject | NFKB2 | |
dc.subject | Inborn errors of immunity | |
dc.title | NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications | |
dc.type | Article | |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9733962/ |