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10.1016/j.jaci.2020.07.033 http://scihub22266oqcxt.onion/10.1016/j.jaci.2020.07.033 32853638!7445138!32853638     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Allergy+Clin+Immunol 2020 ; 146 (5): 1194-1200.e1 Nephropedia Template TP {{tp|p=32853638|t=2020. Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1 |pdf=|usr=}}{{32853638}} gab.com Text Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1 JO: J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=32853638 #FOAvip BACKGROUND: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection. OBJECTIVES: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. METHODS: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs. RESULTS: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children. CONCLUSIONS: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias. Twit Text FOAVip Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1 ????J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=32853638 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32853638 #FOAvip English Wikipedia <ref>{{Cite pmid|32853638}}</ref> Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1 #MMPMID32853638 Lee PY; Platt CD; Weeks S; Grace RF; Maher G; Gauthier K; Devana S; Vitali S; Randolph AG; McDonald DR; Geha RS; Chou J J Allergy Clin Immunol 2020[Nov]; 146 (5): 1194-1200.e1 PMID32853638show ga BACKGROUND: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection. OBJECTIVES: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. METHODS: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs. RESULTS: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children. CONCLUSIONS: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias. |Adolescent[MESH] |Anemia, Hemolytic, Autoimmune/genetics/*immunology/*virology[MESH] |Betacoronavirus[MESH] |COVID-19[MESH] |Child, Preschool[MESH] |Coronavirus Infections/*complications/immunology[MESH] |Haploinsufficiency[MESH] |Humans[MESH] |Male[MESH] |Mutation[MESH] |Pandemics[MESH] |Pneumonia, Viral/*complications/immunology[MESH] |SARS-CoV-2[MESH] |Suppressor of Cytokine Signaling 1 Protein/genetics[MESH] |Systemic Inflammatory Response Syndrome/*immunology/*virology[MESH]Immune dysregulation and multisystem inflammatory syndrome in children(epmc).pdf DeepDyve Pubget Overpricing