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T cell dysfunction and patient age are associated with poor outcomes after mechanical circulatory support device implantation
Authors:Joanna M. Schaenman  Maura Rossetti  Yael Korin  Tiffany Sidwell  Victoria Groysberg  Emily Liang  Sitaram Vangala  Nicholas Wisniewski  Eleanor Chang  Maral Bakir  Galyna Bondar  Martin Cadeiras  Murray Kwon  Elaine F. Reed  Mario Deng
Affiliation:1. Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, United States;2. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, United States;3. UCLA Department of Medicine Statistics Core, David Geffen School of Medicine, Los Angeles, CA 90095, United States;4. Division of Cardiology, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, United States;5. Department of Cardiothoracic Surgery, David Geffen School of Medicine, Los Angeles, CA 90095, United States
Abstract:Immunologic impairment may contribute to poor outcomes after implantation of mechanical circulatory support device (MCSD), with infection often as a terminal event. The study of immune dysfunction is of special relevance given the growing numbers of older patients with heart disease. The aim of the study was to define which immunologic characteristics are associated with development of adverse clinical outcomes after MCSD implantation.We isolated peripheral blood mononuclear cells (PBMC) from patients pre- and up to 20?days post-MCSD implantation and analyzed them by multiparameter flow cytometry for T cell dysfunction, including terminal differentiation, exhaustion, and senescence. We used MELD-XI and SOFA scores measured at each time point as surrogate markers of clinical outcome.Older patients demonstrated increased frequencies of terminally differentiated T cells as well as NKT cells. Increased frequency of terminally differentiated and immune senescent T cells were associated with worse clinical outcome as measured by MELD-XI and SOFA scores, and with progression to infection and death.In conclusion, our data suggest that T cell dysfunction, independently from age, is associated with poor outcomes after MCSD implantation, providing a potential immunologic mechanism behind patient vulnerability to multiorgan dysfunction and death. This noninvasive approach to PBMC evaluation holds promise for candidate evaluation and patient monitoring.
Keywords:MCSD  mechanical circulatory support  PBMC  peripheral blood mononuclear cell  T cell  Immune phenotype  Mechanical circulatory support  Elderly
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