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HGNC Genes

SARS-CoV-2 proteins

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    Impaired ICOS HGNC signaling between Tfh and B cells distinguishes hospitalized from ambulatory CoViD-19 MESHD patients

    Authors: Amanda Hanson; Heather Cohen; Hao Wang; Nandini Shekhar; Chinmayee Shah; Abha Dhaneshwar; Bethany W Harvey; Richard Murray; Christopher J Harvey

    doi:10.1101/2020.12.16.20248343 Date: 2020-12-18 Source: medRxiv

    Emerging evidence suggests that SARS-CoV-2 infections MESHD are characterized by systemic immune responses that appear to be dysregulated MESHD with more severe CoViD-19 disease MESHD. Lymphopenia MESHD and delayed antibody responses are commonly identified in CoViD-19 MESHD subjects, and recent reports have demonstrated abrogation of germinal centers in severe CoViD-19 MESHD. This work assessed a potential mechanistic basis for impaired humoral responses, focusing on the T follicular helper (Tfh) and B cell interface that is critical for germinal center reactions. Here we demonstrated that Tfh activity is impaired in hospitalized relative to ambulatory CoViD-19 MESHD subjects, potentially due to decreased expression of the costimulatory molecule ICOS-L HGNC on B cells. Functional impairment manifested as a diminished ability to stimulated Tfh derived IFN{gamma HGNC} and IL-21 HGNC, the latter of which is critical for B cell proliferation and differentiation. Activation of Tfh cells by agonism of the ICOS HGNC receptor ex vivo by an agonistic antibody stimulated the generation of IFN{gamma HGNC}/ IL-21 HGNC double positive cells from hospitalized CoViD-19 MESHD subjects. This report establishes an immunological defect that differentiates ambulatory from hospitalized CoViD and suggests that agents that could restore impaired mechanisms at the Tfh-B cell interface may be of therapeutic value.

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MeSH Disease
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SARS-CoV-2 Proteins


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