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Your search keyword '"Unterman, Avraham"' showing total 3 results
Start Over Author "Unterman, Avraham" Topic sars-cov-2
3 results on '"Unterman, Avraham"'

1. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.

Author

Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C Jr, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason LE, Ko AI, Montgomery RR, Farhadian SF, Iwasaki A, Shaw AC, van Dijk D, Zhao H, Kleinstein SH, Hafler DA, Kaminski N, and Dela Cruz CS

Subjects
Adaptive Immunity drug effects, Adaptive Immunity genetics, Aged, Antibodies, Monoclonal, Humanized therapeutic use, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, COVID-19 genetics, Cells, Cultured, Female, Gene Expression Regulation drug effects, Gene Expression Regulation immunology, Humans, Immunity, Innate drug effects, Immunity, Innate genetics, Male, RNA-Seq methods, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell immunology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, SARS-CoV-2 drug effects, SARS-CoV-2 physiology, COVID-19 Drug Treatment, Adaptive Immunity immunology, COVID-19 immunology, Gene Expression Profiling methods, Immunity, Innate immunology, SARS-CoV-2 immunology, Single-Cell Analysis methods
Abstract

Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A hi /HLA-DR lo classical monocytes and activated LAG-3 hi T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8 + clones, unmutated IGHG + B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19., (© 2022. The Author(s).)

Published
2022
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2. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Author

Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, and Lucas CL

Subjects
Adolescent, Alarmins immunology, Autoantibodies immunology, CD8-Positive T-Lymphocytes immunology, Child, Child, Preschool, Cytotoxicity, Immunologic genetics, Endothelium immunology, Endothelium pathology, Humans, Killer Cells, Natural immunology, Myeloid Cells immunology, Plasma Cells immunology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Severity of Illness Index, COVID-19 immunology, COVID-19 pathology, SARS-CoV-2 immunology, Systemic Inflammatory Response Syndrome immunology, Systemic Inflammatory Response Syndrome pathology
Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction. MIS-C patients showed elevated expression of cytotoxicity genes in NK and CD8 + T cells and expansion of specific IgG-expressing plasmablasts. Clinically severe MIS-C patients displayed skewed memory T cell TCR repertoires and autoimmunity characterized by endothelium-reactive IgG. The alarmin, cytotoxicity, TCR repertoire, and plasmablast signatures we defined have potential for application in the clinic to better diagnose and potentially predict disease severity early in the course of MIS-C., Competing Interests: Declaration of interests D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available on: https://openpaymentsdata.cms.gov/physician/166753/general-payments. N.K. reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, RohBar in the last 36 months, and Equity in Pliant. N.K. is also a recipient of a grant from Veracyte and non-financial support from Miragen. All outside the submitted work; In addition, N.K. has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech). S.H.K. receives consulting fees from Northrop Grumman. K.B.H. receives consulting fees from Prellis Biologics. B.S. is a former SomaLogic, Inc. (Boulder, CO, USA) employee and a company shareholder. All other authors declared that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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