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  1. Article ; Online: Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine–induced antibody and T cell immunity and function

    Joseph J. Sabatino Jr. / Kristen Mittl / William M. Rowles / Kira McPolin / Jayant V. Rajan / Matthew T. Laurie / Colin R. Zamecnik / Ravi Dandekar / Bonny D. Alvarenga / Rita P. Loudermilk / Chloe Gerungan / Collin M. Spencer / Sharon A. Sagan / Danillo G. Augusto / Jessa R. Alexander / Joseph L. DeRisi / Jill A. Hollenbach / Michael R. Wilson / Scott S. Zamvil /
    Riley Bove

    JCI Insight, Vol 7, Iss

    2022  Volume 4

    Abstract: BACKGROUND Vaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects ...

    Abstract BACKGROUND Vaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses.METHODS Spike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti–spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.RESULTS Anti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb– and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb–treated patients was correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb– and S1P-treated patients. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4+ T cell responses were attenuated.CONCLUSION These findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.FUNDING NIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.
    Keywords Autoimmunity ; COVID-19 ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine-induced antibody and T cell immunity and function.

    Sabatino, Joseph J / Mittl, Kristen / Rowles, William M / McPolin, Kira / Rajan, Jayant V / Laurie, Matthew T / Zamecnik, Colin R / Dandekar, Ravi / Alvarenga, Bonny D / Loudermilk, Rita P / Gerungan, Chloe / Spencer, Collin M / Sagan, Sharon A / Augusto, Danillo G / Alexander, Jessa R / DeRisi, Joseph L / Hollenbach, Jill A / Wilson, Michael R / Zamvil, Scott S /
    Bove, Riley

    JCI insight

    2022  Volume 7, Issue 4

    Abstract: BACKGROUNDVaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects ... ...

    Abstract BACKGROUNDVaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine-specific immunity is needed, including quantitative and functional B and T cell responses.METHODSSpike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti-spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.RESULTSAnti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb- and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb-treated patients was correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb- and S1P-treated patients. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4+ T cell responses were attenuated.CONCLUSIONThese findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.FUNDINGNIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.
    MeSH term(s) Antibodies, Viral/biosynthesis ; Antibodies, Viral/immunology ; COVID-19 Vaccines/immunology ; Humans ; Multiple Sclerosis/immunology ; Multiple Sclerosis/therapy ; SARS-CoV-2/immunology ; T-Lymphocytes/immunology
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines
    Language English
    Publishing date 2022-02-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.156978
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  3. Article ; Online: An autoantibody signature predictive for multiple sclerosis.

    Zamecnik, Colin R / Sowa, Gavin M / Abdelhak, Ahmed / Dandekar, Ravi / Bair, Rebecca D / Wade, Kristen J / Bartley, Christopher M / Kizer, Kerry / Augusto, Danillo G / Tubati, Asritha / Gomez, Refujia / Fouassier, Camille / Gerungan, Chloe / Caspar, Colette M / Alexander, Jessica / Wapniarski, Anne E / Loudermilk, Rita P / Eggers, Erica L / Zorn, Kelsey C /
    Ananth, Kirtana / Jabassini, Nora / Mann, Sabrina A / Ragan, Nicholas R / Santaniello, Adam / Henry, Roland G / Baranzini, Sergio E / Zamvil, Scott S / Sabatino, Joseph J / Bove, Riley M / Guo, Chu-Yueh / Gelfand, Jeffrey M / Cuneo, Richard / von Büdingen, H-Christian / Oksenberg, Jorge R / Cree, Bruce A C / Hollenbach, Jill A / Green, Ari J / Hauser, Stephen L / Wallin, Mitchell T / DeRisi, Joseph L / Wilson, Michael R

    Nature medicine

    2024  

    Abstract: Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to ... ...

    Abstract Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster in approximately 10% of PwMS who share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS. Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active preclinical period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid and serum, where it is highly specific for patients eventually diagnosed with MS. This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes.
    Language English
    Publishing date 2024-04-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-024-02938-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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