Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre- and post-transplantation cytokine responses in stimulated whole blood
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Functional immune reconstitution early after allogeneic haematopoietic cell transplantation : A comparison of pre- and post-transplantation cytokine responses in stimulated whole blood. / Gjærde, Lars Klingen; Brooks, Patrick Terrence; Andersen, Niels Smedegaard; Friis, Lone Smidstrup; Kornblit, Brian; Petersen, Søren Lykke; Schjødt, Ida; Nielsen, Susanne Dam; Ostrowski, Sisse Rye; Sengeløv, Henrik.
I: Scandinavian Journal of Immunology, Bind 94, Nr. 1, e13042, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Functional immune reconstitution early after allogeneic haematopoietic cell transplantation
T2 - A comparison of pre- and post-transplantation cytokine responses in stimulated whole blood
AU - Gjærde, Lars Klingen
AU - Brooks, Patrick Terrence
AU - Andersen, Niels Smedegaard
AU - Friis, Lone Smidstrup
AU - Kornblit, Brian
AU - Petersen, Søren Lykke
AU - Schjødt, Ida
AU - Nielsen, Susanne Dam
AU - Ostrowski, Sisse Rye
AU - Sengeløv, Henrik
N1 - Publisher Copyright: © 2021 The Scandinavian Foundation for Immunology
PY - 2021
Y1 - 2021
N2 - We aimed to use a novel standardized whole-blood stimulation system to evaluate differences in the functional immune reconstitution in patients early after allogeneic haematopoietic cell transplantation (HCT). Between April and September 2018, 30 patients undergoing HCT had whole blood samples collected around day −21 (day 0 being the day of haematopoietic cell infusion) and day +28. Whole blood was transferred to TruCulture assays comprising prefilled incubation tubes with cell culture medium and a standardized stimulus. We used a panel of four stimuli (lipopolysaccharide, resiquimod, heat-killed Candida albicans and polyinosinic:polycytidylic acid) and a blank, designed to evaluate the function of critical extra- and intracellular immunological signalling pathways. For each stimulus, the cytokine response was assessed by the concentration of interferon-γ, interleukin (IL)-12p40, IL-10, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A and tumour necrosis factor-α using a multiplex Luminex assay. Pre-HCT cytokine responses were globally decreased across several different stimuli. Despite patients receiving immunosuppressive prophylaxis at the time, post-HCT cytokine responses were higher and less intercorrelated than pre-HCT responses, also after adjusting for differences in the leukocyte differential counts. For the resiquimod and heat-killed Candida albicans stimuli, we identified a cluster of patients in whom post-HCT responses were lower than average across several cytokines, indicating a possible functional immune deficiency. Our findings suggest that the standardized whole blood stimulation system can be used to reveal heterogeneity in the in vitro cytokine responses to various stimuli after HCT. Larger studies are needed to address if the functional immune reconstitution after HCT can predict the risk of infections.
AB - We aimed to use a novel standardized whole-blood stimulation system to evaluate differences in the functional immune reconstitution in patients early after allogeneic haematopoietic cell transplantation (HCT). Between April and September 2018, 30 patients undergoing HCT had whole blood samples collected around day −21 (day 0 being the day of haematopoietic cell infusion) and day +28. Whole blood was transferred to TruCulture assays comprising prefilled incubation tubes with cell culture medium and a standardized stimulus. We used a panel of four stimuli (lipopolysaccharide, resiquimod, heat-killed Candida albicans and polyinosinic:polycytidylic acid) and a blank, designed to evaluate the function of critical extra- and intracellular immunological signalling pathways. For each stimulus, the cytokine response was assessed by the concentration of interferon-γ, interleukin (IL)-12p40, IL-10, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A and tumour necrosis factor-α using a multiplex Luminex assay. Pre-HCT cytokine responses were globally decreased across several different stimuli. Despite patients receiving immunosuppressive prophylaxis at the time, post-HCT cytokine responses were higher and less intercorrelated than pre-HCT responses, also after adjusting for differences in the leukocyte differential counts. For the resiquimod and heat-killed Candida albicans stimuli, we identified a cluster of patients in whom post-HCT responses were lower than average across several cytokines, indicating a possible functional immune deficiency. Our findings suggest that the standardized whole blood stimulation system can be used to reveal heterogeneity in the in vitro cytokine responses to various stimuli after HCT. Larger studies are needed to address if the functional immune reconstitution after HCT can predict the risk of infections.
KW - allogeneic haematopoietic cell transplantation
KW - cytokine responses
KW - immune reconstitution
U2 - 10.1111/sji.13042
DO - 10.1111/sji.13042
M3 - Journal article
C2 - 33772836
AN - SCOPUS:85104108543
VL - 94
JO - Scandinavian Journal of Immunology, Supplement
JF - Scandinavian Journal of Immunology, Supplement
SN - 0301-6323
IS - 1
M1 - e13042
ER -
ID: 304873236