Browsing by Author "Kerner, G."

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Autoantibodies against type I IFNs in patients with life-threatening COVID-19
    (2020) Bastard, P.; Rosen, L. B.; Zhang, Q.; Michailidis, E.; Hoffmann, H.-H.; Zhang, Y.; Dorgham, K.; Philippot, Q.; Rosain, J.; Béziat, V.; Manry, J.; Shaw, E.; Haljasmägi, L.; Peterson, P.; Lorenzo, L.; Bizien, L.; Trouillet-Assant, S.; Dobbs, K.; Almeida de Jesus, A.; Belot, A.; Kallaste, A.; Catherinot, E.; Tandjaoui-Lambiotte, Y.; Le Pen, J.; Kerner, G.; Bigio, B.; Seeleuthner, Y.; Yang, R.; Bolze, A.; Spaan, A. N.; Delmonte, O. M.; Abers, M. S.; Aiuti, A.; Casari, G.; Lampasona, V.; Piemonti, L.; Ciceri, F.; Bilguvar, K.; Lifton, R. P.; Vasse, M.; Smadja, D. M.; Migaud, M.; Hadjadj, J.; Terrier, B.; Duffy, D.; Quintana-Murci, L.; van de Beek, D.; Roussel, L.; Vinh, D. C.; Tangye, S. G.; Haerynck, F.; Dalmau, D.; Martinez-Picado, J.; Brodin, P.; Nussenzweig, M. C.; Boisson-Dupuis, S.; Rodríguez-Gallego, C.; Vogt, G.; Mogensen, T. H.; Oler, A. J.; Gu, J.; Burbelo, P. D.; Cohen, J. I.; Biondi, A.; Bettini, L. R.; D'Angio, M.; Bonfanti, P.; Rossignol, P.; Mayaux, J.; Rieux-Laucat, F.; Husebye, E. S.; Fusco, F.; Ursini, M. V.; Imberti, L.; Sottini, A.; Paghera, S.; Quiros-Roldan, E.; Rossi, C.; Castagnoli, R.; Montagna, D.; Özçelik, Tayfun; Licari, A.; Marseglia, G. L.; Duval, X.; Ghosn, J.; Tsang, J. S.; Goldbach-Mansky, R.; Kisand, K.; Lionakis, M. S.; Puel, A.; Zhang, S.- Y.; Holland, S. M.; Gorochov, G.; Jouanguy, E.; Rice, C. M.; Cobat, A.; Notarangelo, L. D.; Abel, L.; Su, H. C.; Casanova, J. L.; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort
    Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
  • Thumbnail Image
    ItemOpen Access
    Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant
    (NLM (Medline), 2018) Boisson-Dupuis, S.; Ramirez-Alejo, N.; Li, Z.; Patin, E.; Rao, G.; Kerner, G.; Lim, C. K.; Krementsov, D. N.; Hernandez, N.; Ma, C. S.; Zhang, Q.; Markle, J.; Martinez-Barricarte, R.; Payne, K.; Fisch, R.; Deswarte, C.; Halpern, J.; Bouaziz, M.; Mulwa, J.; Sivanesan, D.; Lazarov, T.; Naves, R.; Garcia, P.; Itan, Y.; Boisson, B.; Checchi, A.; Jabot-Hanin, F.; Cobat, A.; Guennoun, A.; Jackson, C. C.; Pekcan, S.; Çalışkaner, Z.; Inostroza, J.; Costa-Carvalho, B. T.; De Albuquerque, J. A. T.; Garcia-Ortiz, H.; Orozco, L.; Özçelik, Tayfun; Abid, A.; Rhorfi, I. A.; Souhi, H.; Amrani, H. N.; Zegmout, A.; Geissmann, F.; Michnick, S. W.; Muller-Fleckenstein, I.; Fleckenstein, B.; Puel, A.; Ciancanelli, M. J.; Marr, N.; Abolhassani, H.; Balcells, M. E.; Condino-Neto, A.; Strickler, A.; Abarca, K.; Teuscher, C.; Ochs, H. D.; Reisli, I.; Sayar, E. H.; El-Baghdadi, J.; Bustamante, J.; Hammarström, L.; Tangye, S. G.; Pellegrini, S.; Quintana-Murci, L.; Abel, L.; Casanova, J. -L.
    Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common TYK2 P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls (P = 8.37 × 10-8; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of TYK2 selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis. Copyright