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  1. Artikel: Unveiling the autoreactome: Proteome-wide immunological fingerprints reveal the promise of plasma cell depleting therapy.

    Bodansky, Aaron / Yu, David Jl / Rallistan, Alysa / Kalaycioglu, Muge / Boonyaratanakornkit, Jim / Green, Damian J / Gauthier, Jordan / Turtle, Cameron J / Zorn, Kelsey / O'Donovan, Brian / Mandel-Brehm, Caleigh / Asaki, James / Kortbawi, Hannah / Kung, Andrew F / Rackaityte, Elze / Wang, Chung-Yu / Saxena, Aditi / de Dios, Kimberly / Masi, Gianvito /
    Nowak, Richard J / O'Connor, Kevin C / Li, Hao / Diaz, Valentina E / Casaletto, Kaitlin B / Gontrum, Eva Q / Chan, Brandon / Kramer, Joel H / Wilson, Michael R / Utz, Paul J / Hill, Joshua A / Jackson, Shaun W / Anderson, Mark S / DeRisi, Joseph L

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the ... ...

    Abstract The prevalence and burden of autoimmune and autoantibody mediated disease is increasing worldwide, yet most disease etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of proteome-wide autoantibody profiles in both health and disease. We demonstrate that each individual, regardless of disease state, possesses a distinct set of autoreactivities constituting a unique immunological fingerprint, or "autoreactome", that is remarkably stable over years. In addition to uncovering important new biology, the autoreactome can be used to better evaluate the relative effectiveness of various therapies in altering autoantibody repertoires. We find that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly alter an individual's autoreactome, while anti-CD19 and CD-20 therapies have minimal effects, strongly suggesting a rationale for BCMA or other plasma cell targeted therapies in autoantibody mediated diseases.
    Sprache Englisch
    Erscheinungsdatum 2023-12-20
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.12.19.23300188
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity.

    Bodansky, Aaron / Yu, David Jl / Rallistan, Alysa N / Kalaycioglu, Muge / Boonyaratanakornkit, Jim / Green, Damian J / Gauthier, Jordan / Turtle, Cameron J / Zorn, Kelsey C / O'Donovan, Brian / Mandel-Brehm, Caleigh / Asaki, James / Kortbawi, Hannah / Kung, Andrew F / Rackaityte, Elze / Wang, Chung-Yu / Saxena, Aditi / de Dios, Kimberly / Masi, Gianvito /
    Nowak, Richard J / O'Connor, Kevin C / Li, Hao / Diaz, Valentina E / Saloner, Rowan / Casaletto, Kaitlin B / Gontrum, Eva Q / Chan, Brandon J / Kramer, Joel H / Wilson, Michael R / Utz, Paul J / Hill, Joshua A / Jackson, Shaun W / Anderson, Mark S / DeRisi, Joseph L

    The Journal of clinical investigation

    2024  

    Abstract: Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments ... ...

    Abstract Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and CD20 therapies had minimal effects. These data both confirm that the autoreactome is comprised of autoantibodies secreted by plasma cells, and strongly suggest that BCMA or other plasma cell targeting therapies may be highly effective in treating currently refractory autoantibody mediated diseases.
    Sprache Englisch
    Erscheinungsdatum 2024-05-16
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI180012
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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