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  1. Article ; Online: Cellular and Humoral SARS-CoV-2 Vaccination Responses in 192 Adult Recipients of Allogeneic Hematopoietic Cell Transplantation

    Thomas Meyer / Gabriele Ihorst / Ingrid Bartsch / Robert Zeiser / Ralph Wäsch / Hartmut Bertz / Jürgen Finke / Daniela Huzly / Claudia Wehr

    Vaccines, Vol 10, Iss 1782, p

    2022  Volume 1782

    Abstract: To determine factors influencing the vaccination response against SARS-CoV-2 is of importance in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) as they display an increased mortality after SARS-CoV-2 infection, an increased risk ... ...

    Abstract To determine factors influencing the vaccination response against SARS-CoV-2 is of importance in recipients of allogeneic hematopoietic cell transplantation (allo-HCT) as they display an increased mortality after SARS-CoV-2 infection, an increased risk of extended viral persistence and reduced vaccination response. Real-life data on anti-SARS-CoV-2-S1-IgG titers ( n = 192) and IFN-γ release ( n = 110) of allo-HCT recipients were obtained using commercially available, validated assays after vaccination with either mRNA (Comirnaty™, Pfizer-BioNTech™, NY, US and Mainz, Germany or Spikevax™, Moderna™, Cambridge, Massachusetts, US) or vector-based vaccines (Vaxzevria™,AstraZeneca™, Cambridge, UK or Janssen COVID-19 vaccine™Johnson/Johnson, New Brunswick, New Jersey, US), or after a heterologous protocol (vector/mRNA). Humoral response (78% response rate) was influenced by age, time after transplantation, the usage of antithymocyte globulin (ATG) and ongoing immunosuppression, specifically corticosteroids. High counts of B cells during the vaccination period correlated with a humoral response. Only half (55%) of participants showed a cellular vaccination response. It depended on age, time after transplantation, ongoing immunosuppression with ciclosporin A, chronic graft-versus-host disease (cGvHD) and vaccination type, with vector-based protocols favoring a response. Cellular response failure correlated with a higher CD8+ count and activated/HLA-DR+ T cells one year after transplantation. Our data provide the basis to assess both humoral and cellular responses after SARS-CoV2 vaccination in daily practice, thereby opening up the possibility to identify patients at risk.
    Keywords SARS-CoV-2 ; allogeneic hematopoietic cell transplantation (allo-HCT) ; IFN-γ release assay (IGRA) ; specific antibody titer ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease

    Kristina Maas-Bauer / Anna-Verena Stell / Kai-Li Yan / Enrique de Vega / Janaki Manoja Vinnakota / Susanne Unger / Nicolas Núñez / Johana Norona / Nana Talvard-Balland / Stefanie Koßmann / Carsten Schwan / Cornelius Miething / Uta S. Martens / Khalid Shoumariyeh / Rosa P. Nestor / Sandra Duquesne / Kathrin Hanke / Michal Rackiewicz / Zehan Hu /
    Nadia El Khawanky / Sanaz Taromi / Hana Andrlova / Hemin Faraidun / Stefanie Walter / Dietmar Pfeifer / Marie Follo / Johannes Waldschmidt / Wolfgang Melchinger / Michael Rassner / Claudia Wehr / Annette Schmitt-Graeff / Sebastian Halbach / James Liao / Georg Häcker / Tilman Brummer / Joern Dengjel / Geoffroy Andrieux / Robert Grosse / Sonia Tugues / Bruce R. Blazar / Burkhard Becher / Melanie Boerries / Robert Zeiser

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 18

    Abstract: Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help ... ...

    Abstract Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.
    Keywords Science ; Q
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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