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Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (Gzm) are proteases mainly found in cytotoxic lymphocytes that not only have a role in target cell death, but also as mediators of infection and inflammation. In this study we sought to analyse the intracellular expression of GzmA, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected intensive care unit (ICU) patients and 32 healthy controls. Additionally, we measured GzmA and B plasma levels. Both groups of patients presented decreased percentage of natural killer (NK) cells expressing GzmA, B and M relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing GzmB compared to controls. Expression of GzmK remained relatively unaltered between groups. Extracellular levels of GzmB were increased in non-infected ICU patients relative to sepsis patients and healthy controls. Our results show differential alterations in intracellular expression of Gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the Gzm.

Original publication

DOI

10.1111/cei.13601

Type

Journal

Clinical and experimental immunology

Publication Date

08/2021

Volume

205

Pages

222 - 231

Addresses

Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Keywords

Killer Cells, Natural, Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Humans, Sepsis, Critical Illness, Lymphocyte Count, Middle Aged, Female, Male, Granzymes