Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

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buir.contributor.authorÖzçelik, Tayfun
dc.citation.epage26en_US
dc.citation.issueNumber62en_US
dc.citation.spage1en_US
dc.citation.volumeNumber6en_US
dc.contributor.authorBastard, P.
dc.contributor.authorGervais, A.
dc.contributor.authorLe Voyer, T.
dc.contributor.authorRosain, J.
dc.contributor.authorPhilippot, Q.
dc.contributor.authorManry, J.
dc.contributor.authorMichailidis, E.
dc.contributor.authorHoffmann, H. H.
dc.contributor.authorEto, S.
dc.contributor.authorGarcia-Prat, M.
dc.contributor.authorBizien, L.
dc.contributor.authorParra-Martinez, A.
dc.contributor.authorYang, R.
dc.contributor.authorHaljasmagi, L.
dc.contributor.authorMigaud, M.
dc.contributor.authorSarekannu, K.
dc.contributor.authorMaslovskaja, J.
dc.contributor.authorde Prost, N.
dc.contributor.authorTandjaoui-Lambiotte, Y.
dc.contributor.authorLuyt, C. E.
dc.contributor.authorAmador-Borrero, B.
dc.contributor.authorGaudet, A.
dc.contributor.authorPoissy, J.
dc.contributor.authorMorel, P.
dc.contributor.authorRichard, P.
dc.contributor.authorCognasse, F.
dc.contributor.authorTroya, J.
dc.contributor.authorTrouillet-Assant, S.
dc.contributor.authorBelot, A.
dc.contributor.authorSaker, K.
dc.contributor.authorGarcon, P.
dc.contributor.authorRiviere, J. G.
dc.contributor.authorLagier, J. C.
dc.contributor.authorGentile, S.
dc.contributor.authorRosen, L. B.
dc.contributor.authorShaw, E.
dc.contributor.authorMorio, T.
dc.contributor.authorTanaka, J.
dc.contributor.authorDalmau, D.
dc.contributor.authorTharaux, PL.
dc.contributor.authorSene, D.
dc.contributor.authorStepanian, A.
dc.contributor.authorMegarbane, B.
dc.contributor.authorTriantafyllia, V.
dc.contributor.authorFekkar, A.
dc.contributor.authorHeath, J. R.
dc.contributor.authorFranco, JL.
dc.contributor.authorAnaya, J. M.
dc.contributor.authorSole-Violan, J.
dc.contributor.authorImberti, L.
dc.contributor.authorBiondi, A.
dc.contributor.authorBonfanti, P.
dc.contributor.authorCastagnoli, R.
dc.contributor.authorDelmonte, O. M.
dc.contributor.authorZhang, Y.
dc.contributor.authorSnow, A. L.
dc.contributor.authorHolland, S. M.
dc.contributor.authorBiggs, C. M.
dc.contributor.authorMoncada-Velez, M.
dc.contributor.authorArias, A. A.
dc.contributor.authorLorenzo, L.
dc.contributor.authorBoucherit, S.
dc.contributor.authorCoulibaly, B.
dc.contributor.authorAnglicheau, D.
dc.contributor.authorPlanas, A. M.
dc.contributor.authorHaerynck, F.
dc.contributor.authorDuvlis, S.
dc.contributor.authorNussbaum, R. L.
dc.contributor.authorÖzçelik, Tayfun
dc.contributor.authorKeles, S.
dc.contributor.authorBousfiha, A. A.
dc.contributor.authorEl Bakkouri, J.
dc.contributor.authorRamirez-Santana, C.
dc.contributor.authorPaul, S.
dc.contributor.authorPan-Hammarstrom, Q.
dc.contributor.authorHammarstrom, L.
dc.contributor.authorDupont, A.
dc.contributor.authorKurolap, A.
dc.contributor.authorMetz, CN.
dc.contributor.authorAiuti, A.
dc.contributor.authorCasari, G.
dc.contributor.authorLampasona, V.
dc.contributor.authorCiceri, F.
dc.contributor.authorBarreiros, L. A.
dc.contributor.authorDominguez-Garrido, E.
dc.contributor.authorVidigal, M.
dc.contributor.authorZatz, M.
dc.contributor.authorvan de Beek, D.
dc.contributor.authorSahanic, S.
dc.contributor.authorTancevski, I.
dc.contributor.authorStepanovskyy, Y.
dc.contributor.authorBoyarchuk, O.
dc.contributor.authorNukui, Y.
dc.contributor.authorTsumura, M.
dc.contributor.authorVidaur, L.
dc.contributor.authorTangye, S. G.
dc.contributor.authorBurrel, S.
dc.contributor.authorDuffy, D.
dc.contributor.authorQuintana-Murci, L.
dc.contributor.authorKlocperk, A.
dc.contributor.authorKann, N. Y.
dc.contributor.authorShcherbina, A.
dc.contributor.authorLau, Y. L.
dc.contributor.authorLeung, D.
dc.contributor.authorCoulongeat, M.
dc.contributor.authorMarlet, J.
dc.contributor.authorKoning, R.
dc.contributor.authorReyes, L. F.
dc.contributor.authorChauvineau-Grenier, A.
dc.contributor.authorVenet, F.
dc.contributor.authorMonneret, G.
dc.contributor.authorNussenzweig, MC.
dc.contributor.authorArrestier, R.
dc.contributor.authorBoudhabhay, I.
dc.contributor.authorBaris-Feldman, H.
dc.contributor.authorHagin, D.
dc.contributor.authorWauters, J.
dc.contributor.authorMeyts, I.
dc.contributor.authorDyer, A. H.
dc.contributor.authorKennelly, SP.
dc.contributor.authorBourke, N. M.
dc.contributor.authorHalwani, R.
dc.contributor.authorSharif-Askari, N. S.
dc.contributor.authorDorgham, K.
dc.contributor.authorSallette, J.
dc.contributor.authorSedkaoui, S. M.
dc.contributor.authorAlKhater, S.
dc.contributor.authorRigo-Bonnin, R.
dc.contributor.authorMorandeira, F.
dc.contributor.authorRoussel, L.
dc.contributor.authorVinh, DC.
dc.contributor.authorOstrowski, SR.
dc.contributor.authorCondino-Neto, A.
dc.contributor.authorPrando, C.
dc.contributor.authorBondarenko, A.
dc.contributor.authorSpaan, A. N.
dc.contributor.authorGilardin, L.
dc.contributor.authorFellay, J.
dc.contributor.authorLyonnet, S.
dc.contributor.authorBilguvar, K.
dc.contributor.authorLifton, R. P.
dc.contributor.authorMane, S.
dc.contributor.authorAnderson, M. S.
dc.contributor.authorBoisson, B.
dc.contributor.authorBeziat, V.
dc.contributor.authorZhang, SY.
dc.contributor.authorAndreakos, E.
dc.contributor.authorHermine, O.
dc.contributor.authorPujol, A.
dc.contributor.authorPeterson, P.
dc.contributor.authorMogensen, T. H.
dc.contributor.authorRowen, L.
dc.contributor.authorMond, J.
dc.contributor.authorDebette, S.
dc.contributor.authorde Lamballerie, X.
dc.contributor.authorDuval, X.
dc.contributor.authorMentre, F.
dc.contributor.authorZins, M.
dc.contributor.authorSoler-Palacin, P.
dc.contributor.authorColobran, R.
dc.contributor.authorGorochov, G.
dc.contributor.authorSolanich, X.
dc.contributor.authorSusen, S.
dc.contributor.authorMartinez-Picado, J.
dc.contributor.authorRaoult, D.
dc.contributor.authorVasse, M.
dc.contributor.authorGregersen, P. K.
dc.contributor.authorPiemonti, L.
dc.contributor.authorRodriguez-Gallego, C.
dc.contributor.authorNotarangelo, LD.
dc.contributor.authorSu, H. C.
dc.contributor.authorKisand, K.
dc.contributor.authorOkada, S.
dc.contributor.authorPuel, A.
dc.contributor.authorJouanguy, E.
dc.contributor.authorRice, C. M.
dc.contributor.authorTiberghien, P.
dc.contributor.authorZhang, Q.
dc.contributor.authorCobat, A.
dc.contributor.authorAbel, L.
dc.contributor.authorCasanova, J. L.
dc.date.accessioned2022-01-27T08:55:18Z
dc.date.available2022-01-27T08:55:18Z
dc.date.issued2021-08-20
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractCirculating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.en_US
dc.description.provenanceSubmitted by Türkan Cesur (cturkan@bilkent.edu.tr) on 2022-01-27T08:55:18Z No. of bitstreams: 1 Autoantibodies_neutralizing_type_I_IFNs_are_present_in_~4%_of_uninfected_individuals_over_70_years_old_and_account_for_~20%_of_COVID-19_deaths.pdf: 4626941 bytes, checksum: 50adec8d688d957570d57ef595bcd924 (MD5)en
dc.description.provenanceMade available in DSpace on 2022-01-27T08:55:18Z (GMT). No. of bitstreams: 1 Autoantibodies_neutralizing_type_I_IFNs_are_present_in_~4%_of_uninfected_individuals_over_70_years_old_and_account_for_~20%_of_COVID-19_deaths.pdf: 4626941 bytes, checksum: 50adec8d688d957570d57ef595bcd924 (MD5) Previous issue date: 2021-08-20en
dc.identifier.doi10.1126/sciimmunol.abl4340en_US
dc.identifier.eissn2470-9468
dc.identifier.urihttp://hdl.handle.net/11693/76825
dc.language.isoEnglishen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofhttps://doi.org/10.1126/sciimmunol.abl4340en_US
dc.source.titleScience Immunologyen_US
dc.titleAutoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deathsen_US
dc.typeArticleen_US

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