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Browsing by Author "Chen, Jinguo"

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    Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome
    (2024) Walitt, Brian; Singh, Komudi; LaMunion, Samuel; Hallett , Mark; Jacobson, Steve; Chen, Kong; Enose-Akahata, Yoshimi; Apps, Richard; Barb, Jennifer; Bedard, Patrick; Brychta, Robert; Buckley, Ashura; Burbelo, Peter; Calco, Brice; Cathay, Brianna; Chen, Li; Chigurupati, Snigdha; Chen, Jinguo; Cheung, Foo; Chin, Lisa; Coleman, Benjamin; Courville, Amber; Deming, Madeleine; Drinkard, Bart; Feng, Li; Ferrucci, Luigi; Gabel, Scott; Gavin, Angelique; Goldstein, David; Hassanzadeh, Shahin; Horan, Sean; Horovitz, Silvina; Johnson, Kory; Govan, Anita; Knutson, Kristine; Kreskow, Joy; Levin, Mark; Lyons, Jonathan; Madian, Nicholas; Vial Undurraga, Felipe
    Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.
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    Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19
    (2022) Sacco , Keith; Castagnoli , Riccardo; Vakkilainen, Svetlana; Liu, Can; Delmonte, Ottavia M.; Oguz, Cihan; Kaplan, Ian M.; Alehashemi, Sara; Burbelo, Peter D.; Bhuyan, Farzana; Jesus, Adriana A.; Dobbs , Kerry; Rosen, Lindsey B.; Cheng, Aristine; Shaw, Elana; Vakkilainen, Mikko S.; Pala , Francesca; Lack, Justin; Zhang, Yu; Fink, Danielle L.; Oikonomou, Vasileios; Snow , Andrew L.; Dalgard, Clifton L.; Chen, Jinguo; Sellers, Brian A.; Montealegre Sanchez, Gina A.; Barron, Karyl; Rey-Jurado, Emma; Vial, Cecilia; Poli, Cecilia; Licari, Amelia; Montagna, Daniela; Marseglia, Gian Luigi
    Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n= 110) and MIS-C (n= 76), along with pediatric healthy controls (pHCs; n= 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

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