Citations 2
Germline mutations in a G protein identify signaling cross-talk in T cells
Ham, Hyoungjun , Jing, Huie , Lamborn, Ian T. , Kober, M. , Anderson, David E. , Druey, Kirk M. , Mandl, Judith N. , Isidor, Bertrand , Freeman, Alexandra F. , Ganesan, Sundar , Karsak, Meliha , Mustillo, Peter , Teo, Juliana , Zolkipli‐Cunningham, Zarazuela , Lecoquierre, François , Schmid, Jana Pachlopnik , Kuhns, Douglas B. , Xu, Xuehua , Al–Herz, Waleed , Terhal, Paulien A., Muurinen, Mari , Barlogis, Vincent , Danielson, Jeffrey J. , Stewart, Helen , Rading, Sebastian, Keren, Boris , Pfundt, Rolph , Potocki, Lorraine , Olivier, Kenneth N., Faivre, Laurence , Wong, Melanie , Puel, Anne , Chou, Janet , Tusseau, Maud, Moutsopoulos, Niki M. , Matthews, Helen, Simons, Cas , Fink, Danielle , Kong, Heidi H. , Kabát, Juraj , Kim, Woo Sung , Bierhals, Tatjana , Meguro, Kazuyuki , Gu, Jingwen , Stoddard, Jennifer , Banos-Pinero, Benito, Slack, Maria A., Trivellin, Giampaolo , Mazel, Benoît , Li, Samuel T. , Watts, Val J. , Rodriguez-Quevedo, Maria F. , Bruel, Ange‐Line , Lehalle, Daphné , Torres, Daniel , Sullivan, Kathleen E. , Duffourd, Yannis, Similuk, Morgan , Blanc, Pierre , Jin, Tian, Geha, Raif S., Casanova, Jean‐Laurent , Mäkitie, Outi , Edery, Patrick , Germain, Ronald N. , Billadeau, Daniel D. , Zhang, Yu , Lenardo, Michael J. , Kober, Megan M , Koval, Alexey , Anderson, D Eric , Druey, Kirk M , Mandl, Judith N , Isidor, Bertrand , Ferreira, Carlos R , Freeman, Alexandra F , Karsak, Meliha , Mustillo, Peter J , Teo, Juliana , Chatron, Nicolas , Lecoquierre, Francois , Oler, Andrew J , Schmid, Jana Pachlopnik , Kuhns, Douglas B , Xu, Xuehua , Hauck, Fabian , Al-Herz, Waleed , Wagner, Matias , Terhal, Paulien A , Muurinen, Mari , Barlogis, Vincent , Loid, Petra , Keren, Boris , Pfundt, Rolph , Zarember, Kol A , Vill, Katharina , Olivier, Kenneth N , Lesca, Gaetan , Faivre, Laurence , Puel, Anne , Chou, Janet , Moutsopoulos, Niki M , Simons, Cas , Soldatos, Ariane , Masle-Farquhar, Etienne , Pittaluga, Stefania , Brink, Robert , Kong, Heidi H , Kabat, Juraj , Bierhals, Tatjana , Hsu, Amy P. , Gu, Jingwen , Trivellin, Giampaolo , Mazel, Benoît , Soomann, Maarja , Li, Samuel , Watts, Val J , Stratakis, Constantine A , Rodriguez-Quevedo, Maria F , Bruel, Ange-Line , Lipsanen-Nyman, Marita , Saultier, Paul , Lehalle, Daphne , Torres, Daniel , Barbarot, Sébastien , Neu, Axel , Similuk, Morgan N , McWalter, Kirsty , Blanc, Pierre , Bézieau, Stéphane , Geha, Raif S , Casanova, Jean Laurent , Makitie, Outi M , Edery, Patrick , Christodoulou, John , Germain, Ronald N , Goodnow, Christopher C , Sakmar, Thomas P , Billadeau, Daniel D , Kury, Sebastien , Katanaev, Vladimir L , Zhang, Yu , Lenardo, Michael J , Su, Helen C , Berchiche, Yamina A. , Wagner, Matias , Cruz, Phillip , Lesca, Gaëtan , Tusseau, Maud , Taft, Ryan J. , Pittaluga, Stefania , Baños-Piñero, Benito, Stratakis, Constantine A. , Jain, Rashmi, Bezieau, Stéphane , Jin, Tian , Kubisch, Christian , Küry, Sébastien , Su, Helen C.
Science | September 19, 2024 | Volume: 385 | Issue: 6715 | Pages: No page available
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)–activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)–AKT S6 signaling to drive cellular growth and proliferation.
Pre-existing Immunocompromising Conditions and Outcomes of Acute COVID-19 Patients Admitted for Pediatric Intensive Care
Rowan, Courtney M. , Zambrano, Laura D. , Newhams, Margaret M. , Kücükak, Suden, McNamara, Elizabeth R, Mack, Elizabeth H. , Fitzgerald, Julie C. , Irby, Katherine , Schuster, Jennifer E. , Kong, Michele, Loftis, Laura L. , Kolmar, Amanda , Babbitt, Christopher , Nofziger, Ryan A. , Hall, Mark W. , Gertz, Shira J. , Zinter, Matt S. , Halasa, Natasha , Bradford, Tamara T. , McLaughlin, Gwenn E., Singh, Aalok R. , Staat, Mary Allen , Coates, Bria M. , Crandall, Hillary R, Maamari, Mia , Havlin, Kevin , Schwarz, Adam J. , Carroll, Christopher L. , Levy, Emily R. , Campbell, Angela P. , Randolph, Adrienne G. , Chou, Janet , Investigators, Overcoming COVID-19, Kong, Michele, Gaspers, Mary Glas , Sanders, Ronald C., Schwarz, Adam J, Harvey, Helen , Port, Emily, Shankman, Sara, Mansour, Rachel, Espinal, Paula S., Tarquinio, Keiko M. , Bhoojhawon, Guru , Sullivan, Janice E, Bradford, Tamara T, Newhams, Margaret M, Chen, Sabrina , Young, Cameron C, Carroll, Ryan W. , Yager, Phoebe H. , Flori, Heidi R. , Johnson, Brandi A., Drapeau, Noelle M., Malloch, Lacy , Martin, Lora, McGraw, Sarah , Schuster, Jennifer E, Cullimore, Melissa L. , Clouser, Katharine N. , Kleinman, Lawrence C. , Horwitz, Steven M. , Kuebler, Joseph D. , Soma, Vijaya L, Doymaz, Sule , Schwartz, Stephanie P, Walker, Tracie C. , Lansell, Amanda , Hall, Mark W. , Burnett, Ryan H., Bush, Jenny L., Carcillo, Joseph A. , Butler, Andrew , Reed, Nelson, Stewart, Laura S , Golchha, Meena, Samperio, Marian, Qurashi, Jacob , Bowens, Cindy , Crandall, Hillary , Smith, Lincoln , Kong, Michele , Martin, Lora , Randolph, Adrienne G , Levy, Emily R , Kong, Michele , Staat, Mary A , Gertz, Shira J , LaBere, Brenna , Young, Cameron C. , Maddux, Aline B. , Kong, Michele, Dapul, Heda , Schwartz, Stephanie P. , Bembea, Melania M. , Cvijanovich, Natalie Z , Hobbs, Charlotte V. , Wellnitz, Kari , Moffitt, Kristin , Investigators, Overcoming COVID-19, Kong, Michele, Typpo, Katri , Schwarz, Adam J, Pannaraj, Pia S. , Giuliano, John S. , Michelson, Kelly Nicole , Sullivan, Janice E, Montgomery, Vicki , Bradford, Tamara T, Graciano, Ana Lía , Newhams, Margaret M, Young, Cameron C, Son, Mary Beth F. , Fernandes, Neil D. , Hume, Janet R. , Behl, Supriya , McGraw, Sarah, Schuster, Jennifer E, Spinella, Philip C. , McCulloh, Russell J. , Li, Simon , Ratner, Adam J. , BIAGAS, KATHERINE V. , Schwartz, Stephanie P, Shein, Steven L. , Bush, Jenny, Thomas, Neal J. , Fink, Ericka L. , Reed, Nelson, Muñoz, Álvaro Coronado , McGuire, John K.
Clinical Infectious Diseases | March 11, 2024 | Volume: 79 | Issue: 2 | Pages: 395-404
Abstract Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.