Details

Autor(en) / Beteiligte

• Bodansky, Aaron
• Vazquez, Sara E.
• Chou, Janet
• Novak, Tanya
• Al-Musa, Amer
• Young, Cameron
• Newhams, Margaret
• Kucukak, Suden
• Zambrano, Laura D.
• Mitchell, Anthea
• Wang, Chung-Yu
• Moffitt, Kristin
• Halasa, Natasha B.
• Loftis, Laura L.
• Schwartz, Stephanie P.
• Walker, Tracie C.
• Mack, Elizabeth H.
• Fitzgerald, Julie C.
• Gertz, Shira J.
• Rowan, Courtney M.
• Irby, Katherine
• Sanders, Ronald C.
• Kong, Michele
• Schuster, Jennifer E.
• Staat, Mary A.
• Zinter, Matt S.
• Cvijanovich, Natalie Z.
• Tarquinio, Keiko M.
• Coates, Bria M.
• Flori, Heidi R.
• Dahmer, Mary K.
• Crandall, Hillary
• Cullimore, Melissa L.
• Levy, Emily R.
• Chatani, Brandon
• Nofziger, Ryan
• Yates, Masson
• Smith, Chelsea
• Zinter, MattS
• McLaughlin, Gwenn
• Randolph, Adrienne G.
• Newhams, Margaret M.
• Moon, Hye Kyung
• Kobayashi, Takuma
• Melo, Jeni
• Chen, Sabrina R.
• Behl, Supriya
• Drapeau, Noelle M.
• McCulloh, Russell J.
• Nofziger, Ryan A.
• Staat, Mary Allen
• Rohlfs, Chelsea C.
• Reed, Nelson
• Geha, Raif S.
• DeRisi, Joseph
• Campbell, Angela P.
• Anderson, Mark

Titel

NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2–related complications

Ist Teil von

• Journal of allergy and clinical immunology, 2023-04, Vol.151 (4), p.926-930.e2

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. 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. 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. 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. 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.