Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

被引：197

作者：

Bastard, Paul ^{[1
,2
,3
]}

Orlova, Elizaveta ^{[4
]}

Sozaeva, Leila ^{[4
]}

Levy, Romain ^{[1
,2
,5
]}

James, Alyssa ^{[6
]}

Schmitt, Monica M. ^{[6
]}

Ochoa, Sebastian ^{[6
]}

Kareva, Maria ^{[4
]}

Rodina, Yulia ^{[7
]}

Gervais, Adrian ^{[1
,2
]}

Le Voyer, Tom ^{[1
,2
]}

Rosain, Jeremie ^{[1
,2
]}

Philippot, Quentin ^{[1
,2
]}

Neehus, Anna-Lena ^{[1
,2
]}

Shaw, Elana ^{[6
]}

Migaud, Melanie ^{[1
]}

Bizien, Lucy ^{[1
]}

Ekwall, Olov ^{[8
,9
]}

Berg, Stefan ^{[8
]}

Beccuti, Guglielmo ^{[10
]}

Ghizzoni, Lucia ^{[10
]}

Thiriez, Gerard ^{[11
]}

Pavot, Arthur ^{[12
]}

Goujard, Cecile ^{[13
]}

Fremond, Marie-Louise ^{[5
,14
]}

Carter, Edwin ^{[15
]}

Rothenbuhler, Anya ^{[16
]}

Linglart, Agnes ^{[16
]}

Mignot, Brigite ^{[17
]}

Comte, Aurelie ^{[17
]}

Cheikh, Nathalie ^{[18
]}

Hermine, Olivier ^{[2
,19
]}

Breivik, Lars ^{[20
,21
]}

Husebye, Eystein S. ^{[20
,21
,22
,23
]}

Humbert, Sebastien ^{[24
]}

Rohrlich, Pierre ^{[25
]}

Coaquette, Alain ^{[26
]}

Vuoto, Fanny ^{[27
]}

Faure, Karine ^{[27
]}

Mahlaoui, Nizar ^{[5
,28
]}

Kotnik, Primoz ^{[29
,30
]}

Battelino, Tadej ^{[29
,30
]}

Podkrajsek, Katarina Trebusak ^{[29
,30
]}

Kisand, Kai ^{[31
]}

Ferre, Elise M. N. ^{[6
]}

DiMaggio, Thomas ^{[6
]}

Rosen, Lindsey B. ^{[6
]}

Burbelo, Peter D. ^{[32
]}

McIntyre, Martin ^{[33
]}

Kann, Nelli Y. ^{[7
]}

机构：

[1] Necker Hosp Sick Children, INSERM, Necker Branch, Lab Human Genet Infect Dis,U1163, Paris, France

[2] Univ Paris, Imagine Inst, Paris, France

[3] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, 1230 York Ave, New York, NY 10021 USA

[4] Endocrinol Res Ctr, Moscow, Russia

[5] Necker Hosp Sick Children, AP HP, Pediat Immunol Hematol & Rheumatol Unit, Paris, France

[6] NIAID, Lab Clin Immunol & Microbiol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[7] Dmitry Rogachev Natl Med Res Ctr Pediat Hematol O, Moscow, Russia

[8] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden

[9] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden

[10] Univ Turin, Dept Med Sci, Turin, Italy

[11] Besancon Hosp, Intens Care Unit, Besancon, France

[12] Kremlin Bicetre Hosp, Intens Care Unit, Le Kremlin Bicetre, France

[13] Paris Saclay Univ, Bicetre Hosp, AP HP, INSERM,Internal Med Dept,U1018, Le Kremlin Bicetre, France

[14] Univ Paris, Imagine Inst, Lab Neurogenet & Neuroinflammat, Paris, France

[15] MRC, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland

[16] Paris Saclay Univ, Bicetre Hosp, AP HP, Pediat Endocrinol Dept, Le Kremlin Bicetre, France

[17] Univ Hosp Besancon, Pediat Med Unit, Besancon, France

[18] Univ Hosp Besancon, Pediat Hematol Unit, Besancon, France

[19] Univ Paris, Necker Hosp Sick Children, AP HP, Hematol Dept, Paris, France

[20] Univ Bergen, Dept Clin Sci, Bergen, Norway

[21] Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway

[22] Haukeland Hosp, Dept Med, Bergen, Norway

[23] Karolinska Inst, Dept Med Solna, Stockholm, Sweden

[24] Besancon Hosp, Internal Med Unit, Besancon, France

[25] CHU Nice, Pediat Hematol & Oncol Unit, Nice, France

[26] Besancon Hosp, Lab Virol, Besancon, France

[27] Lille Hosp, Infect Dis Unit, Lille, France

[28] Hop Univ Necker Enfants Malades, AP HP, Ctr Reference Deficits Immunitaires Hereditaires, Paris, France

[29] Univ Ljubljana, Fac Med, Ljubljana, Slovenia

[30] Univ Childrens Hosp, Univ Med Ctr Ljubljana, Ljubljana, Slovenia

[31] Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia

[32] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA

[33] Royal Alexandra Hosp, Paisley, Renfrew, Scotland

[34] Sechenov Univ, Dept Endocrinol 1, Moscow, Russia

[35] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[36] Howard Hughes Med Inst, New York, NY 10065 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2021年 / 218卷 / 07期

基金：

俄罗斯科学基金会;

关键词：

CHRONIC MUCOCUTANEOUS CANDIDIASIS; AUTOIMMUNE REGULATOR; INBORN-ERRORS; INTERFERONS; MUTATIONS; AIRE; TOLERANCE; DISEASE;

D O I：

10.1084/jem.20210554

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-alpha subtypes and/or IFN-w; one had anti-IFN-8 and another anti-IFN-E, but none had anti-IFN-K. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.

引用

页数：19

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