Nature · 2023

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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Le Voyer Tom, Parent Audrey V, Liu Xian, Cederholm Axel, Gervais Adrian, Rosain Jérémie, Nguyen Tina, Perez Lorenzo Malena, Rackaityte Elze, Rinchai Darawan, Zhang Peng, Bizien Lucy, Hancioglu Gonca, Ghillani-Dalbin Pascale, Charuel Jean-Luc, Philippot Quentin, Gueye Mame Sokhna, Maglorius Renkilaraj Majistor Raj Luxman, Ogishi Masato, Soudée Camille, Migaud Mélanie, Rozenberg Flore, Momenilandi Mana, Riller Quentin, Imberti Luisa, Delmonte Ottavia M, Müller Gabriele, Keller Baerbel, Orrego Julio, Franco Gallego William Alexander, Rubin Tamar, Emiroglu Melike, Parvaneh Nima, Eriksson Daniel, Aranda-Guillen Maribel, Berrios David I, Vong Linda, Katelaris Constance H, Mustillo Peter, Raedler Johannes, Bohlen Jonathan, Bengi Celik Jale, Astudillo Camila, Winter Sarah, NF-κB Consortium, COVID Human Genetic Effort, McLean Catriona, Guffroy Aurélien, DeRisi Joseph L, Yu David, Miller Corey, Feng Yi, Guichard Audrey, Béziat Vivien, Bustamante Jacinta, Pan-Hammarström Qiang, Zhang Yu, Rosen Lindsey B, Holland Steve M, Bosticardo Marita, Kenney Heather, Castagnoli Riccardo, Slade Charlotte A, Boztuğ Kaan, Mahlaoui Nizar, Latour Sylvain, Abraham Roshini S, Lougaris Vassilios, Hauck Fabian, Sediva Anna, Atschekzei Faranaz, Sogkas Georgios, Poli M Cecilia, Slatter Mary A, Palterer Boaz, Keller Michael D, Pinzon-Charry Alberto, Sullivan Anna, Droney Luke, Suan Daniel, Wong Melanie, Kane Alisa, Hu Hannah, Ma Cindy, Grombiříková Hana, Ciznar Peter, Dalal Ilan, Aladjidi Nathalie, Hie Miguel, Lazaro Estibaliz, Franco Jose, Keles Sevgi, Malphettes Marion, Pasquet Marlene, Maccari Maria Elena, Meinhardt Andrea, Ikinciogullari Aydan, Shahrooei Mohammad, Celmeli Fatih, Frosk Patrick, Goodnow Christopher C, Gray Paul E, Belot Alexandre, Kuehn Hye Sun, Rosenzweig Sergio D, Miyara Makoto, Licciardi Francesco, Servettaz Amélie, Barlogis Vincent, Le Guenno Guillaume, Herrmann Vera-Maria, Kuijpers Taco, Ducoux Grégoire, Sarrot-Reynauld Françoise, Schuetz Catharina, Cunningham-Rundles Charlotte, Rieux-Laucat Frédéric, Tangye Stuart G, Sobacchi Cristina, Doffinger Rainer, Warnatz Klaus, Grimbacher Bodo, Fieschi Claire, Berteloot Laureline, Bryant Vanessa L, Trouillet Assant Sophie, Su Helen, Neven Benedicte, Abel Laurent, Zhang Qian, Boisson Bertrand, Cobat Aurélie, Jouanguy Emmanuelle, Kampe Olle, Bastard Paul, Roifman Chaim M, Landegren Nils, Notarangelo Luigi D, Anderson Mark S, Casanova Jean-Laurent, Puel Anne

Аннотация

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

Предметные рубрики MeSH

Autoantibodies Genetic Predisposition to Disease Pneumonia, Viral NF-kappa B p52 Subunit AIRE Protein NF-kappaB-Inducing Kinase I-kappa B Proteins Loss of Function Mutation Gain of Function Mutation Interferon Type I NF-kappa B COVID-19 Thyroid Epithelial Cells Humans Heterozygote Thymus Gland Transcription Factor RelB Polyendocrinopathies, Autoimmune

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH