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149 results on '"Zhou, Qinhua"'

4. Cellular Mechanisms Underlying B Cell Abnormalities in Patients With Gain-of-Function Mutations in the PIK3CD Gene

Author

Wang, Wenjie, Min, Qing, Lai, Nannan, Csomos, Krisztian, Wang, Ying, Liu, Luyao, Meng, Xin, Sun, Jinqiao, Hou, Jia, Ying, Wenjing, Zhou, Qinhua, Sun, Bijun, Hui, Xiaoying, Ujhazi, Boglarka, Gordon, Sumai, Buchbinder, David, Schuetz, Catharina, Butte, Manish, Walter, Jolan E, Wang, Xiaochuan, and Wang, Ji-Yang

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Class I Phosphatidylinositol 3-Kinases, Gain of Function Mutation, Immunoglobulin M, Mutation, Phosphatidylinositol 3-Kinases, activated PI3K delta syndrome, B cell survival and activation, CD27(-)IgD(-) double-negative B cells, Ig gene class switch recombination, plasma cell differentiation, CD27-IgD- double-negative B cells, activated PI3Kδ syndrome, Medical Microbiology, Biochemistry and cell biology
Abstract

BackgroundActivated phosphoinositide 3 kinase (PI3K) -delta syndrome (APDS) is an inborn error of immunity with variable clinical phenotype of immunodeficiency and immune dysregulation and caused by gain-of-function mutations in PIK3CD. The hallmark of immune phenotype is increased proportions of transitional B cells and plasmablasts (PB), progressive B cell loss, and elevated levels of serum IgM.ObjectiveTo explore unique B cell subsets and the pathomechanisms driving B cell dysregulation beyond the transitional B cell stage in APDS.MethodsClinical and immunological data was collected from 24 patients with APDS. In five cases, we performed an in-depth analysis of B cell phenotypes and cultured purified naïve B cells to evaluate their survival, activation, Ig gene class switch recombination (CSR), PB differentiation and antibody secretion. We also analyzed PB differentiation capacity of sorted CD27-IgD- double-negative B (DNB) cells.ResultsThe patients had increased B cell sizes and higher proportions of IgM+ DNB cells than healthy controls (HC). Their naïve B cells exhibited increased death, impaired CSR but relatively normal PB differentiation. Upon stimulation, patient's DNB cells secreted a similar level of IgG but a higher level of IgM than DNB cells from HC. Targeted therapy of PI3K inhibition partially restored B cell phenotypes.ConclusionsThe present study suggests additional mechanistic insight into B cell pathology of APDS: (1) decreased peripheral B cell numbers may be due to the increased death of naïve B cells; (2) larger B cell sizes and expanded DNB population suggest enhanced activation and differentiation of naïve B cells into DNB cells; (3) the impaired CSR yet normal PB differentiation can predominantly generate IgM-secreting cells, resulting in elevated IgM levels.

Published
2022

5. Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria

Author

Bohlen, Jonathan, Zhou, Qinhua, Philippot, Quentin, Ogishi, Masato, Rinchai, Darawan, Nieminen, Tea, Seyedpour, Simin, Parvaneh, Nima, Rezaei, Nima, Yazdanpanah, Niloufar, Momenilandi, Mana, Conil, Clément, Neehus, Anna-Lena, Schmidt, Carltin, Arango-Franco, Carlos A., Voyer, Tom Le, Khan, Taushif, Yang, Rui, Puchan, Julia, Erazo, Lucia, Roiuk, Mykola, Vatovec, Taja, Janda, Zarah, Bagarić, Ivan, Materna, Marie, Gervais, Adrian, Li, Hailun, Rosain, Jérémie, Peel, Jessica N, Seeleuthner, Yoann, Han, Ji Eun, L’Honneur, Anne-Sophie, Moncada-Vélez, Marcela, Martin-Fernandez, Marta, Horesh, Michael E., Kochetkov, Tatiana, Schmidt, Monika, AlShehri, Mohammed A., Salo, Eeva, Saxen, Harri, ElGhazali, Gehad, Yatim, Ahmad, Soudée, Camille, Sallusto, Federica, Ensser, Armin, Marr, Nico, Zhang, Peng, Bogunovic, Dusan, Cobat, Aurélie, Shahrooei, Mohammad, Béziat, Vivien, Abel, Laurent, Wang, Xiaochuan, Boisson-Dupuis, Stéphanie, Teleman, Aurelio A., Bustamante, Jacinta, Zhang, Qian, and Casanova, Jean-Laurent

Published
2023
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8. Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

Author

Wu, Qi, Sun, Bijun, Hou, Jia, Hui, Xiaoying, Wang, Chenghao, Wang, Wenjie, Ying, Wenjing, Liu, Luyao, Zhu, Li, Wang, Ying, Li, Qifan, Yu, Meiping, Zhou, Weitao, Chen, Yao, Wu, Bingbing, Sun, Jinqiao, Zhou, Qinhua, Qian, Feng, and Wang, Xiaochuan

Subjects
HERPES simplex, GENETIC variation, FETAL diseases, ROTAVIRUS diseases, T cells
Abstract

Objective: FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism. Methods: Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis. Results: The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment. Conclusions: We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Facile preparation of thermally conductive fiber film by self‐assembling interconnected boron nitride nanosheets for effective thermal interface materials.

Author

Ye, Bin, Li, Ling, Dai, Kun, Xie, Zuoxiang, Zhou, Qinhua, Dong, Yuyang, Zheng, Qingbin, Park, Soo‐Jin, and Zhang, Yinhang

Subjects
THERMAL interface materials, XANTHAN gum, THERMOELECTRIC generators, THERMAL conductivity, NANOSTRUCTURED materials, BORON nitride
Abstract

Boron nitride (BN) has garnered significant attention for its potential in developing thermally conductive materials owing to its inherent insulating properties and high thermal conductivity. However, achieving high thermal conductivity in bulk materials or 3D structures constructed by BN sheets has remained challenging. In this study, we present a novel approach to design a high‐quality BN fiber using xanthan gum (XG) as a skeleton, aiming to facilitate heat dissipation in integrated circuits. The resulting thermally conductive film, with orderly and compactly arranged BN sheets in the XG skeleton, exhibits a remarkable in‐plane thermal conductivity of 8.26 Wm−1 K−1 and an out‐of‐plane thermal conductivity of 1.35 Wm−1 K−1. This film efficiently enables fast heat dissipation for LED chips and thermoelectric generators. Finite element simulation further supports the efficient heat transfer capacity of the BN fiber films. Highlights: A high‐quality BN fiber was prepared by a facile approach.The BN fiber film exhibited high thermal conductivity.This film enables fast heat dissipation in practical applications. [ABSTRACT FROM AUTHOR]

Published
2024
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10. The spectrum of bacterial infectionin a large cohort of Chinese pediatric patients with inborn errors of immunity: a nine-year, retrospective, single-center study

Author

Zhu, Xiaodan, primary, Fu, Pan, additional, Wang, Wenjie, additional, Ying, Wenjing, additional, Sun, Bijun, additional, Hou, Jia, additional, Hui, Xiaoying, additional, Sun, Jinqiao, additional, Wang, Chuanqing, additional, Zhou, Qinhua, additional, and Wang, Xiaochuan, additional

Published
2023
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18. Diagnosis of mixed infection and a primary immunodeficiency disease using next-generation sequencing: a case report

Author

Zhang, Xiaolei, primary, Wang, Yixue, additional, Pen, Daly, additional, Liu, Jing, additional, Zhou, Qinhua, additional, Wang, Yao, additional, Zhong, Huaqing, additional, Liu, Tingyan, additional, Chen, Weiming, additional, Wu, Bingbing, additional, Zhou, Yang, additional, Wang, Chuanqing, additional, Li, Xiangyu, additional, Yu, Fangyou, additional, Wang, Xiaochuan, additional, Lu, Guoping, additional, and Yan, Gangfeng, additional

Published
2023
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27. Rapid diagnosis of Talaromyces marneffei infection by metagenomic next-generation sequencing technology in a Chinese cohort of inborn errors of immunity

Author

Liu, Lipin, primary, Sun, Bijun, additional, Ying, Wenjing, additional, Liu, Danru, additional, Wang, Ying, additional, Sun, Jinqiao, additional, Wang, Wenjie, additional, Yang, Mi, additional, Hui, Xiaoying, additional, Zhou, Qinhua, additional, Hou, Jia, additional, and Wang, Xiaochuan, additional

Published
2022
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29. Cellular Mechanisms Underlying B Cell Abnormalities in Patients With Gain-of-Function Mutations in the PIK3CD Gene

Author

Wang, Wenjie, primary, Min, Qing, additional, Lai, Nannan, additional, Csomos, Krisztian, additional, Wang, Ying, additional, Liu, Luyao, additional, Meng, Xin, additional, Sun, Jinqiao, additional, Hou, Jia, additional, Ying, Wenjing, additional, Zhou, Qinhua, additional, Sun, Bijun, additional, Hui, Xiaoying, additional, Ujhazi, Boglarka, additional, Gordon, Sumai, additional, Buchbinder, David, additional, Schuetz, Catharina, additional, Butte, Manish, additional, Walter, Jolan E., additional, Wang, Xiaochuan, additional, and Wang, Ji-Yang, additional

Published
2022
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30. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author

Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Laouénan, Cédric [0000-0002-3681-6314], Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jeremie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Hraiech, Sami, COVID Human Genetic Effort, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Ciancanelli, Michael J., Laouénan, Cédric, COVID-STORM Clinicians, COVID Clinicians, Gorochov, Guy, Imagine COVID Group, French COVID Cohort Study Group, NIAID-USUHS/TAGC COVID Immunity Group, Snow, Andrew L., Dalgard, Clifton L., Milner, Joshua D., Vinh, Donald C., Meyts, Isabelle, Mogensen, Trine, Marr, Nico, Béziat, Vivien, Bilguvar, Kaya, Spaan, András N., Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Ye, Junqiang, Nussenzweig, Michel C., Jouanguy, Emmanuelle, García-Sastre, Adolfo, Krammer, Florian, Smith, Nikaïa, Pujol, Aurora, Duffy, Darragh, Lifton, Richard P., Zhang, Shen-Ying, Bolze, Alexandre, Sancho-Shimizu, Vanessa, Rice, Charles M., Schneider, William M., Abel, Laurent, Notarangelo, Luigi D., Cobat, Aurélie, Zhang, Peng, Su, Helen C., Casanova, Jean-Laurent, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Razooky, Brandon S., Onodi, Fanny, Korniotis, Sarantis, Rapaport, Franck, Karpf, Lea, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Jin Eun, Lorenzo, Lazaro, Seeleuthner, Yoann, Bizien, Lucy, Meade, Philip, Biondi, Andrea, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Manry, Jérémy, Masson, Cecile, Schmitt, Yoann, Bettini, Laura Rachele, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Smits, Guillaume, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F., Mansouri, Davood, Al-Saud, Haya, D'Angio, Mariella, Al-Mulla, Fahd, Almourfi, Feras, Migeotte, Isabelle, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Haerynck, Filomeen, Rossi, Camillo, Oler, Andrew J., CoV-Contact Cohort, Tompkins, Miranda F., Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Amsterdam UMC Covid-19 Biobank, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Puel, Anne, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Laouénan, Cédric [0000-0002-3681-6314], Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jeremie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Hraiech, Sami, COVID Human Genetic Effort, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Ciancanelli, Michael J., Laouénan, Cédric, COVID-STORM Clinicians, COVID Clinicians, Gorochov, Guy, Imagine COVID Group, French COVID Cohort Study Group, NIAID-USUHS/TAGC COVID Immunity Group, Snow, Andrew L., Dalgard, Clifton L., Milner, Joshua D., Vinh, Donald C., Meyts, Isabelle, Mogensen, Trine, Marr, Nico, Béziat, Vivien, Bilguvar, Kaya, Spaan, András N., Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Ye, Junqiang, Nussenzweig, Michel C., Jouanguy, Emmanuelle, García-Sastre, Adolfo, Krammer, Florian, Smith, Nikaïa, Pujol, Aurora, Duffy, Darragh, Lifton, Richard P., Zhang, Shen-Ying, Bolze, Alexandre, Sancho-Shimizu, Vanessa, Rice, Charles M., Schneider, William M., Abel, Laurent, Notarangelo, Luigi D., Cobat, Aurélie, Zhang, Peng, Su, Helen C., Casanova, Jean-Laurent, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Razooky, Brandon S., Onodi, Fanny, Korniotis, Sarantis, Rapaport, Franck, Karpf, Lea, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Jin Eun, Lorenzo, Lazaro, Seeleuthner, Yoann, Bizien, Lucy, Meade, Philip, Biondi, Andrea, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Manry, Jérémy, Masson, Cecile, Schmitt, Yoann, Bettini, Laura Rachele, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Smits, Guillaume, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F., Mansouri, Davood, Al-Saud, Haya, D'Angio, Mariella, Al-Mulla, Fahd, Almourfi, Feras, Migeotte, Isabelle, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Haerynck, Filomeen, Rossi, Camillo, Oler, Andrew J., CoV-Contact Cohort, Tompkins, Miranda F., Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Amsterdam UMC Covid-19 Biobank, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Puel, Anne, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, and Karabela, Şemsi Nur

Abstract

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Published
2020

31. Human genetic and immunological determinants of critical COVID-19 pneumonia

Author

Zhang, Qian, Bastard, Paul, Karbuz, Adem, Gervais, Adrian, Tayoun, Ahmad Abou, Aiuti, Alessandro, Belot, Alexandre, Bolze, Alexandre, Gaudet, Alexandre, Bondarenko, Anastasiia, Liu, Zhiyong, Spaan, András, Guennoun, Andrea, Arias, Andres Augusto, Planas, Anna, Sediva, Anna, Shcherbina, Anna, Neehus, Anna-Lena, Puel, Anne, Froidure, Antoine, Novelli, Antonio, Parlakay, Aslınur Özkaya, Pujol, Aurora, Yahşi, Aysun, Gülhan, Belgin, Bigio, Benedetta, Boisson, Bertrand, Drolet, Beth, Franco, Carlos Andres Arango, Flores, Carlos, Rodríguez-Gallego, Carlos, Prando, Carolina, Biggs, Catherine, Luyt, Charles-Edouard, Dalgard, Clifton, O’Farrelly, Cliona, Matuozzo, Daniela, Dalmau, David, Perlin, David, Mansouri, Davood, van de Beek, Diederik, Vinh, Donald, Dominguez-Garrido, Elena, Hsieh, Elena, Erdeniz, Emine Hafize, Jouanguy, Emmanuelle, Şevketoglu, Esra, Talouarn, Estelle, Quiros-Roldan, Eugenia, Andreakos, Evangelos, Husebye, Eystein, Alsohime, Fahad, Haerynck, Filomeen, Casari, Giorgio, Novelli, Giuseppe, Aytekin, Gökhan, Morelle, Guillaume, Alkan, Gulsum, Bayhan, Gulsum Iclal, Feldman, Hagit Baris, Su, Helen, von Bernuth, Horst, Resnick, Igor, Bustos, Ingrid, Meyts, Isabelle, Migeotte, Isabelle, Tancevski, Ivan, Bustamante, Jacinta, Fellay, Jacques, El Baghdadi, Jamila, Martinez-Picado, Javier, Casanova, Jean-Laurent, Rosain, Jeremie, Manry, Jeremy, Chen, Jie, Christodoulou, John, Bohlen, Jonathan, Franco, José Luis, Li, Juan, Anaya, Juan Manuel, Rojas, Julian, Ye, Junqiang, Uddin, K., Yasar, Kadriye Kart, Kisand, Kai, Okamoto, Keisuke, Chaïbi, Khalil, Mironska, Kristina, Maródi, László, Abel, Laurent, Renia, Laurent, Lorenzo, Lazaro, Hammarström, Lennart, Ng, Lisa, Quintana-Murci, Lluis, Erazo, Lucia Victoria, Notarangelo, Luigi, Reyes, Luis Felipe, Allende, Luis, Imberti, Luisa, Renkilaraj, Majistor Raj Luxman Maglorius, Moncada-Velez, Marcela, Materna, Marie, Anderson, Mark, Gut, Marta, Chbihi, Marwa, Ogishi, Masato, Emiroglu, Melike, Seppänen, Mikko, Uddin, Mohammed, Shahrooei, Mohammed, Alexander, Natalie, Hatipoglu, Nevin, Marr, Nico, Akçay, Nihal, Boyarchuk, Oksana, Slaby, Ondrej, Akcan, Ozge Metin, Zhang, Peng, Soler-Palacín, Pere, Gregersen, Peter, Brodin, Petter, Garçon, Pierre, Morange, Pierre-Emmanuel, Pan-Hammarström, Qiang, Zhou, Qinhua, Philippot, Quentin, Halwani, Rabih, de Diego, Rebeca Perez, Levy, Romain, Yang, Rui, Öz, Şadiye Kübra Tüter, Muhsen, Saleh Al, Kanık-Yüksek, Saliha, Espinosa-Padilla, Sara, Ramaswamy, Sathishkumar, Okada, Satoshi, Bozdemir, Sefika Elmas, Aytekin, Selma Erol, Karabela, Şemsi Nur, Keles, Sevgi, Senoglu, Sevtap, Zhang, Shen-Ying, Duvlis, Sotirija, Constantinescu, Stefan, Boisson-Dupuis, Stephanie, Turvey, Stuart, Tangye, Stuart, Asano, Takaki, Ozcelik, Tayfun, Le Voyer, Tom, Maniatis, Tom, Morio, Tomohiro, Mogensen, Trine, Sancho-Shimizu, Vanessa, Beziat, Vivien, Solanich, Xavier, Bryceson, Yenan, Lau, Yu-Lung, Itan, Yuval, Cobat, Aurélie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Effort, COVID Human Genetic, Özçelik, Tayfun, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Yale University, Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, European Commission, Square Foundation, Ministère de l’Enseignement supérieur et de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondation Bettencourt Schueller, Regione Lazio, National Institute of Allergy and Infectious Diseases (US), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-20-COV6-0001,CRISPR-TARGET-CoV,Cribles CRISPR à l'échelle du génome pour identifier de nouvelles cibles thérapeutiques et inhiber la réplication du SARS-CoV-2(2020), Zhang, Q., Bastard, P., Karbuz, A., Gervais, A., Tayoun, A. A., Aiuti, A., Belot, A., Bolze, A., Gaudet, A., Bondarenko, A., Spaan, A. N., Guennoun, A., Arias, A. A., Planas, A. M., Sediva, A., Shcherbina, A., Neehus, A. -L., Puel, A., Froidure, A., Novelli, A., Parlakay, A. O., Pujol, A., Yahsi, A., Gulhan, B., Bigio, B., Boisson, B., Drolet, B. A., Franco, C. A. A., Flores, C., Rodriguez-Gallego, C., Prando, C., Biggs, C. M., Luyt, C. -E., Dalgard, C. L., O'Farrelly, C., Matuozzo, D., Dalmau, D., Perlin, D. S., Mansouri, D., van de Beek, D., Vinh, D. C., Dominguez-Garrido, E., Hsieh, E. W. Y., Erdeniz, E. H., Jouanguy, E., Sevketoglu, E., Talouarn, E., Quiros-Roldan, E., Andreakos, E., Husebye, E., Alsohime, F., Haerynck, F., Casari, G., Novelli, G., Aytekin, G., Morelle, G., Alkan, G., Bayhan, G. I., Feldman, H. B., Su, H. C., von Bernuth, H., Resnick, I., Bustos, I., Meyts, I., Migeotte, I., Tancevski, I., Bustamantem, J., Fellay, J., El Baghdadi, J., Martinez-Picado, J., Casanova, J. -L., Rosain, J., Manry, J., Chen, J., Christodoulou, J., Bohlen, J., Franco, J. L., Li, J., Anaya, J. M., Rojas, J., Ye, J., Uddin, K. M. F., Yasar, K. K., Kisand, K., Okamoto, K., Chaibi, K., Mironska, K., Marodi, L., Abel, L., Renia, L., Lorenzo, L., Hammarstrom, L., Ng, L. F. P., Quintana-Murci, L., Erazo, L. V., Notarangelo, L. D., Reyes, L. F., Allende, L. M., Imberti, L., Renkilaraj, M. R. L. M., Moncada-Velez, M., Materna, M., Anderson, M. S., Gut, M., Chbihi, M., Ogishi, M., Emiroglu, M., Seppanen, M. R. J., Uddin, M. J., Shahrooei, M., Alexander, N., Hatipoglu, N., Marr, N., Akcay, N., Boyarchuk, O., Slaby, O., Akcan, O. M., Zhang, P., Soler-Palacin, P., Gregersen, P. K., Brodin, P., Garcon, P., Morange, P. -E., Pan-Hammarstrom, Q., Zhou, Q., Philippot, Q., Halwani, R., de Diego, R. P., Levy, R., Yang, R., Oz, S. K. T., Muhsen, S. A., Kanik-Yuksek, S., Espinosa-Padilla, S., Ramaswamy, S., Okada, S., Bozdemir, S. E., Aytekin, S. E., Karabela, S. N., Keles, S., Senoglu, S., Zhang, S. -Y., Duvlis, S., Constantinescu, S. N., Boisson-Dupuis, S., Turvey, S. E., Tangye, S. G., Asano, T., Ozcelik, T., Le Voyer, T., Maniatis, T., Morio, T., Mogensen, T. H., Sancho-Shimizu, V., Beziat, V., Solanich, X., Bryceson, Y., Lau, Y. -L., Itan, Y., and Cobat, A.

Subjects
Multidisciplinary, [SDV]Life Sciences [q-bio], Critical Illness, COVID-19, Dendritic Cells, Article, Toll-Like Receptor 3, Basic medicine, Age Distribution, Toll-Like Receptor 7, Settore MED/03, Interferon Type I, Humans, Autoantibodies, Genome-Wide Association Study, Sex Distribution
Abstract

COVID Human Genetic Effort: Adem Karbuz, Adrian Gervais, Ahmad Abou Tayoun, Alessandro Aiuti, Alexandre Belot, Alexandre Bolze, Alexandre Gaudet, Anastasiia Bondarenko, Zhiyong Liu, András N. Spaan, Andrea Guennoun, Andres Augusto Arias, Anna M. Planas, Anna Sediva, Anna Shcherbina, Anna-Lena Neehus, Anne Puel, Antoine Froidure, Antonio Novelli, Aslınur Özkaya Parlakay, Aurora Pujol, Aysun Yahşi, Belgin Gülhan, Benedetta Bigio, Bertrand Boisson, Beth A. Drolet, Carlos Andres Arango Franco, Carlos Flores, Carlos Rodríguez-Gallego, Carolina Prando, Catherine M. Biggs, Charles-Edouard Luyt, Clifton L. Dalgard, Cliona O’Farrelly, Daniela Matuozzo, David Dalmau, David S. Perlin, Davood Mansouri, Diederik van de Beek, Donald C. Vinh, Elena Dominguez-Garrido, Elena W. Y. Hsieh, Emine Hafize Erdeniz, Emmanuelle Jouanguy, Esra Şevketoglu, Estelle Talouarn, Eugenia Quiros-Roldan, Evangelos Andreakos, Eystein Husebye, Fahad Alsohime, Filomeen Haerynck, Giorgio Casari, Giuseppe Novelli, Gökhan Aytekin, Guillaume Morelle, Gulsum Alkan, Gulsum Iclal Bayhan, Hagit Baris Feldman, Helen C. Su, Horst von Bernuth, Igor Resnick, Ingrid Bustos, Isabelle Meyts, Isabelle Migeotte, Ivan Tancevski, Jacinta Bustamante, Jacques Fellay, Jamila El Baghdadi, Javier Martinez-Picado, Jean-Laurent Casanova, Jeremie Rosain, Jeremy Manry, Jie Chen, John Christodoulou, Jonathan Bohlen, José Luis Franco, Juan Li, Juan Manuel Anaya, Julian Rojas, Junqiang Ye, K. M. Furkan Uddin, Kadriye Kart Yasar, Kai Kisand, Keisuke Okamoto, Khalil Chaïbi, Kristina Mironska, László Maródi, Laurent Abel, Laurent Renia, Lazaro Lorenzo, Lennart Hammarström, Lisa F. P. Ng, Lluis Quintana-Murci, Lucia Victoria Erazo, Luigi D. Notarangelo, Luis Felipe Reyes, Luis M. Allende, Luisa Imberti, Majistor Raj Luxman Maglorius Renkilaraj, Marcela Moncada-Velez, Marie Materna, Mark S. Anderson, Marta Gut, Marwa Chbihi, Masato Ogishi, Melike Emiroglu, Mikko R. J. Seppänen, Mohammed J. Uddin, Mohammed Shahrooei, Natalie Alexander, Nevin Hatipoglu, Nico Marr, Nihal Akçay, Oksana Boyarchuk, Ondrej Slaby, Ozge Metin Akcan, Peng Zhang, Pere Soler-Palacín, Peter K. Gregersen, Petter Brodin, Pierre Garçon, Pierre-Emmanuel Morange, Qiang Pan-Hammarström, Qinhua Zhou, Quentin Philippot, Rabih Halwani, Rebeca Perez de Diego, Romain Levy, Rui Yang, Şadiye Kübra Tüter Öz, Saleh Al Muhsen, Saliha Kanık-Yüksek, Sara Espinosa-Padilla, Sathishkumar Ramaswamy, Satoshi Okada, Sefika Elmas Bozdemir, Selma Erol Aytekin, Şemsi Nur Karabela, Sevgi Keles, Sevtap Senoglu, Shen-Ying Zhang, Sotirija Duvlis, Stefan N. Constantinescu, Stephanie Boisson-Dupuis, Stuart E. Turvey, Stuart G. Tangye, Takaki Asano, Tayfun Ozcelik, Tom Le Voyer, Tom Maniatis, Tomohiro Morio, Trine H. Mogensen, Vanessa Sancho-Shimizu, Vivien Beziat, Xavier Solanich, Yenan Bryceson, Yu-Lung Lau & Yuval Itan, SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the ‘Investments for the Future’ program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR grant GENVIR (ANR-20-CE93-003), ANR AABIFNCOV (ANR-20-CO11-0001) and ANR MIS-C (ANR 21-COVR-0039, GenMIS-C) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir—Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, The French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. P.B. was supported by the FRM (EA20170638020) and the MD-PhD programme of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). G.N. is supported by Regione Lazio (Research Group Projects 2020) no. A0375-2020-36663, GecoBiomark. H.C.S. and L.D.N. are supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Published
2022

34. RAG1 splicing mutation causes enhanced B cell differentiation and autoantibody production

Author

Min, Qing, primary, Meng, Xin, additional, Zhou, Qinhua, additional, Wang, Ying, additional, Li, Yaxuan, additional, Lai, Nannan, additional, Xiong, Ermeng, additional, Wang, Wenjie, additional, Yasuda, Shoya, additional, Yu, Meiping, additional, Zhang, Hai, additional, Sun, Jinqiao, additional, Wang, Xiaochuan, additional, and Wang, Ji-Yang, additional

Published
2021
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35. Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

Author

Sun, Bijun, Zhu, Zeyu, Hui, Xiaoying, Sun, Jinqiao, Wang, Wenjie, Ying, Wenjing, Zhou, Qinhua, Yao, Haili, Hou, Jia, and Wang, Xiaochuan

Subjects
CHRONIC granulomatous disease, BCG vaccines, MYCOBACTERIAL diseases, MYCOBACTERIUM tuberculosis, DIAGNOSTIC errors
Abstract

Purpose: We aimed to report the clinical and immunological characteristics of variant type X91+ chronic granulomatous disease (CGD) in a Chinese cohort. Methods: The clinical manifestations and immunological phenotypes of patients with X91+ CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phox protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry. Results: Patients with X91+ CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91+ CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections. Mycobacterium tuberculosis infection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91+ CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91+ CGD, X91− CGD, and X910 CGD) was statistically significant (P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency. CYBB mutations associated with X91+ CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91+ CGD–related mutations (c.1462–2 A > T, c.1243C > T, and c.925G > A) were identified. Conclusions: Variant type X91+ CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91+ CGD to prevent missed diagnoses. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author

Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K D, Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Bilguvar, Kaya, Ye, Junqiang, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Onodi, Fanny, Korniotis, Sarantis, Karpf, Léa, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M, Razooky, Brandon S, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Ji Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Seeleuthner, Yoann, Manry, Jeremy, Masson, Cecile, Schmitt, Yohann, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F, Mansouri, Davood, Al-Saud, Haya, Al-Mulla, Fahd, Almourfi, Feras, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, van de Beek, Diederik, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Oler, Andrew J, Tompkins, Miranda F, Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Smits, Guillaume, Migeotte, Isabelle, Haerynck, Filomeen, Soler-Palacin, Pere, Martin-Nalda, Andrea, Colobran, Roger, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Gallego, Carlos Rodríguez, Novelli, Giuseppe, Hraiech, Sami, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Laouénan, Cédric, Snow, Andrew L, Dalgard, Clifton L, Milner, Joshua, Vinh, Donald C, Mogensen, Trine H, Marr, Nico, Spaan, András N, Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Puel, Anne, Ciancanelli, Michael, Meyts, Isabelle, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Nussenzweig, Michel, García-Sastre, Adolfo, Krammer, Florian, Pujol, Aurora, Duffy, Darragh, Lifton, Richard, Zhang, Shen-Ying, Gorochov, Guy, Béziat, Vivien, Jouanguy, Emmanuelle, Sancho-Shimizu, Vanessa, Rice, Charles M, Abel, Laurent, Notarangelo, Luigi D, Cobat, Aurélie, Su, Helen C, Casanova, Jean-Laurent, Pesci, Alberto, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Zhang, Qian, Bastard, Paul, Liu, Zhiyong, Le Pen, Jérémie, Moncada-Velez, Marcela, Chen, Jie, Ogishi, Masato, Sabli, Ira K D, Hodeib, Stephanie, Korol, Cecilia, Rosain, Jérémie, Bilguvar, Kaya, Ye, Junqiang, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Zhang, Yu, Onodi, Fanny, Korniotis, Sarantis, Karpf, Léa, Philippot, Quentin, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M, Razooky, Brandon S, Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Moens, Leen, Han, Ji Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Corneau, Aurélien, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Seeleuthner, Yoann, Manry, Jeremy, Masson, Cecile, Schmitt, Yohann, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Li, Juan, Fellay, Jacques, Roussel, Lucie, Shahrooei, Mohammad, Alosaimi, Mohammed F, Mansouri, Davood, Al-Saud, Haya, Al-Mulla, Fahd, Almourfi, Feras, Al-Muhsen, Saleh Zaid, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, van de Beek, Diederik, Biondi, Andrea, Bettini, Laura Rachele, D'Angio, Mariella, Bonfanti, Paolo, Imberti, Luisa, Sottini, Alessandra, Paghera, Simone, Quiros-Roldan, Eugenia, Rossi, Camillo, Oler, Andrew J, Tompkins, Miranda F, Alba, Camille, Vandernoot, Isabelle, Goffard, Jean-Christophe, Smits, Guillaume, Migeotte, Isabelle, Haerynck, Filomeen, Soler-Palacin, Pere, Martin-Nalda, Andrea, Colobran, Roger, Morange, Pierre-Emmanuel, Keles, Sevgi, Çölkesen, Fatma, Ozcelik, Tayfun, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Gallego, Carlos Rodríguez, Novelli, Giuseppe, Hraiech, Sami, Tandjaoui-Lambiotte, Yacine, Duval, Xavier, Laouénan, Cédric, Snow, Andrew L, Dalgard, Clifton L, Milner, Joshua, Vinh, Donald C, Mogensen, Trine H, Marr, Nico, Spaan, András N, Boisson, Bertrand, Boisson-Dupuis, Stéphanie, Bustamante, Jacinta, Puel, Anne, Ciancanelli, Michael, Meyts, Isabelle, Maniatis, Tom, Soumelis, Vassili, Amara, Ali, Nussenzweig, Michel, García-Sastre, Adolfo, Krammer, Florian, Pujol, Aurora, Duffy, Darragh, Lifton, Richard, Zhang, Shen-Ying, Gorochov, Guy, Béziat, Vivien, Jouanguy, Emmanuelle, Sancho-Shimizu, Vanessa, Rice, Charles M, Abel, Laurent, Notarangelo, Luigi D, Cobat, Aurélie, Su, Helen C, Casanova, Jean-Laurent, and Pesci, Alberto

Abstract

Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Published
2020

44. A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1

Author

Tao, Panfeng, primary, Sun, Jinqiao, additional, Wu, Zheming, additional, Wang, Shihao, additional, Wang, Jun, additional, Li, Wanjin, additional, Pan, Heling, additional, Bai, Renkui, additional, Zhang, Jiahui, additional, Wang, Ying, additional, Lee, Pui Y., additional, Ying, Wenjing, additional, Zhou, Qinhua, additional, Hou, Jia, additional, Wang, Wenjie, additional, Sun, Bijun, additional, Yang, Mi, additional, Liu, Danru, additional, Fang, Ran, additional, Han, Huan, additional, Yang, Zhaohui, additional, Huang, Xin, additional, Li, Haibo, additional, Deuitch, Natalie, additional, Zhang, Yuan, additional, Dissanayake, Dilan, additional, Haude, Katrina, additional, McWalter, Kirsty, additional, Roadhouse, Chelsea, additional, MacKenzie, Jennifer J., additional, Laxer, Ronald M., additional, Aksentijevich, Ivona, additional, Yu, Xiaomin, additional, Wang, Xiaochuan, additional, Yuan, Junying, additional, and Zhou, Qing, additional

Published
2019
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46. A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.

Author

Tao, Panfeng, Sun, Jinqiao, Wu, Zheming, Wang, Shihao, Wang, Jun, Li, Wanjin, Pan, Heling, Bai, Renkui, Zhang, Jiahui, Wang, Ying, Lee, Pui Y., Ying, Wenjing, Zhou, Qinhua, Hou, Jia, Wang, Wenjie, Sun, Bijun, Yang, Mi, Liu, Danru, Fang, Ran, and Han, Huan

Abstract

Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethality during mouse development2,3. However, the functional importance of blocking caspase-8-mediated cleavage of RIPK1 on RIPK1 activation in humans is unknown. Here we identify two families with variants in RIPK1 (D324V and D324H) that lead to distinct symptoms of recurrent fevers and lymphadenopathy in an autosomal-dominant manner. Impaired cleavage of RIPK1 D324 variants by caspase-8 sensitized patients' peripheral blood mononuclear cells to RIPK1 activation, apoptosis and necroptosis induced by TNF. The patients showed strong RIPK1-dependent activation of inflammatory signalling pathways and overproduction of inflammatory cytokines and chemokines compared with unaffected controls. Furthermore, we show that expression of the RIPK1 mutants D325V or D325H in mouse embryonic fibroblasts confers not only increased sensitivity to RIPK1 activation-mediated apoptosis and necroptosis, but also induction of pro-inflammatory cytokines such as IL-6 and TNF. By contrast, patient-derived fibroblasts showed reduced expression of RIPK1 and downregulated production of reactive oxygen species, resulting in resistance to necroptosis and ferroptosis. Together, these data suggest that human non-cleavable RIPK1 variants promote activation of RIPK1, and lead to an autoinflammatory disease characterized by hypersensitivity to apoptosis and necroptosis and increased inflammatory response in peripheral blood mononuclear cells, as well as a compensatory mechanism to protect against several pro-death stimuli in fibroblasts. A dominantly inherited human autoinflammatory disease caused by mutations in RIPK1 is identified, and RIPK1 mutations that prevent caspase-8 cleavage sensitize cells to apoptosis, necroptosis and inflammation. [ABSTRACT FROM AUTHOR]

Published
2020
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48. Pristimerin Inhibits LPS-Triggered Neurotoxicity in BV-2 Microglia Cells Through Modulating IRAK1/TRAF6/TAK1-Mediated NF-κB and AP-1 Signaling Pathways In Vitro.

Author

Hui, Bin, Zhang, Liping, Zhou, Qinhua, and Hui, Ling

Subjects
TREATMENT of neurodegeneration, TRITERPENOIDS, ANTIOXIDANTS, ANTINEOPLASTIC agents, MICROGLIA, NEUROTOXICOLOGY, PREVENTION, THERAPEUTICS
Abstract

Microglia plays a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations and secreting inflammatory molecules. However, hyperactivated microglial is neurotoxic and plays critical roles in the pathogenesis of neurodegenerative diseases. Pristimerin, a naturally occurring triterpenoid, possesses antitumor, antioxidant, and anti-inflammatory activities. However, the effect and the molecular mechanism of pristimerin against lipopolysaccharide (LPS)-induced neurotoxicity in microglia remain to be revealed. In the present study, using BV-2 microglial cultures, we investigated whether pristimerin modifies neurotoxicity after LPS stimulation and which intracellular pathways are involved in the effect of pristimerin. Here we show that pristimerin markedly suppressed the release of Regulated on Activation, Normal T Expressed and Secreted (RANTES), transforming growth factor-β1 (TGF-β1), IL-6, tumor necrosis factor-α (TNF-α), and nitric oxide (NO). Pristimerin also significantly inhibited migration of BV-2 microglia and alleviated the death of neuron-like PC12 cell induced by the conditioned medium from LPS-activated BV-2 microglial cells. Moreover, pristimerin reduced the expression and interaction of TNF Receptor-Associated Factor 6 (TRAF6) and Interleukin-1 Receptor-Associated Kinases (IRAK1), limiting TGF-beta activating kinase 1 (TAK1) activation, and resulting in an inhibition of IKKα/β/NF-κB and MKK7/JNK/AP-1 signaling pathway in LPS-activated BV-2 microglia. Taken together, the anti-neurotoxicity action of pristimerin is mediated through the inhibition of TRAF6/IRAK1/TAK1 interaction as well as the related pathways: IKKα/β/NF-κB and MKK7/JNK/AP-1 signaling pathways. These findings may suggest that pristimerin might serve as a new therapeutic agent for treating hyperactivated microglial induced neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Published
2018
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