作者
Stéphanie Boisson-Dupuis, Noe Ramirez-Alejo, Zhi Li, Etienne Patin, Geetha Rao, Gaspard Kerner, Che Kang Lim, Dimitry N Krementsov, Nicholas Hernandez, Cindy S Ma, Qian Zhang, Janet Markle, Ruben Martinez-Barricarte, Kathryn Payne, Robert Fisch, Caroline Deswarte, Joshua Halpern, Matthieu Bouaziz, Jeanette Mulwa, Durga Sivanesan, Tomi Lazarov, Rodrigo Naves, Patricia Garcia, Yuval Itan, Bertrand Boisson, Alix Checchi, Fabienne Jabot-Hanin, Aurélie Cobat, Andrea Guennoun, Carolyn C Jackson, Sevgi Pekcan, Zafer Caliskaner, Jaime Inostroza, Beatriz Tavares Costa-Carvalho, Jose Antonio Tavares de Albuquerque, Humberto Garcia-Ortiz, Lorena Orozco, Tayfun Ozcelik, Ahmed Abid, Ismail Abderahmani Rhorfi, Hicham Souhi, Hicham Naji Amrani, Adil Zegmout, Frédéric Geissmann, Stephen W Michnick, Ingrid Muller-Fleckenstein, Bernhard Fleckenstein, Anne Puel, Michael J Ciancanelli, Nico Marr, Hassan Abolhassani, María Elvira Balcells, Antonio Condino-Neto, Alexis Strickler, Katia Abarca, Cory Teuscher, Hans D Ochs, Ismail Reisli, Esra H Sayar, Jamila El-Baghdadi, Jacinta Bustamante, Lennart Hammarström, Stuart G Tangye, Sandra Pellegrini, Lluis Quintana-Murci, Laurent Abel, Jean-Laurent Casanova
发表日期
2018/12/21
期刊
Science immunology
卷号
3
期号
30
页码范围
eaau8714
出版商
American Association for the Advancement of Science
简介
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 …
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