CD4 T-cell function assay using Cylex ImmuKnow and lymphocyte subset recovery following allogeneic hematopoietic stem cell transplantation

Jo, Yong-Jun; Lim, Jihyang; Kim, Yonggoo; Han, Kyungja; Min, Woo-Sung; Oh, Eun‐Jee

doi:10.1016/j.trim.2015.09.001

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…The Cylex ImmuKnow ® is another immune monitoring assay, which after stimulation with PHA measures intracellular adenosine triphosphate levels in CD4+ T-cells ( 24 ). Several studies in the HSCT population did not demonstrate any additional clinical value of the ImmunKnow assay ( 11 , 25 , 26 ). More complex biomarkers such as T-cell immunoglobulin and mucin-domain containing 3 (TIM3), interleukin-6, soluble tumor necrosis factor receptor 1, and plasma suppression of tumorigenicity 2 have shown some promise in predicting AGVHD and NRM ( 3 , 5 ).…”

Section: Discussionmentioning

confidence: 96%

Low T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2017

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BackgroundSuccessful engraftment and reconstitution of the innate and adaptive immune system are associated with improved outcomes in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). A clinically meaningful and simple biomarker of immunosuppression could potentially assist clinicians in their decision-making. We aimed to determine the relationship between T-cell production of interferon gamma (IFN-γ) in response to phytohemagglutinin (PHA) to clinical outcomes in HSCT recipients.MethodsA prospective observational multicenter study of 73 adult allogeneic HSCT recipients was conducted in Melbourne, Australia. Eligible participants were >18 years and at risk of cytomegalovirus disease. T-cell responses to PHA were assessed at 3, 6, 9, and 12 months post-HSCT using the commercial quantiferon-cytomegalovirus assay, which quantifies IFN-γ production by ELISA following stimulation with PHA. A low response was defined as IFN-γ <0.5 IU/ml following stimulation with PHA.ResultsAt 3 months post-HSCT, high responses to PHA (median IFN-γ 7.68 IU/ml) were seen in 63% of participants and low responses to PHA (median IFN-γ 0.06 IU/ml) in 37%. IFN-γ responses to PHA were significantly associated with the severity of acute graft versus host disease (AGVHD) (spearman r = −0.53, p < 0.001) and correlated with blood lymphocyte count (spearman r = 0.52, p < 0.001). Twelve month overall survival was greater in individuals with high compared to low IFN-γ response to PHA at 3 months [92 vs. 62%, respectively, Cox proportional hazard ratio (HR): 4.12 95% CI: 1.2–13.7, p = 0.02]. Non-relapse mortality (NRM) was higher in individuals with low IFN-γ response to PHA (competing risk regression HR 11.6 p = 0.02). In individuals with no AGVHD compared to AGVHD and high IFN-γ response to PHA compared to AGVHD and low IFN-γ response to PHA, 12-month survival was 100 vs. 80 vs. 52%, respectively (log rank test p < 0.0001).ConclusionLow IFN-γ response to PHA at the 3-month time-point following allogeneic HSCT was predictive of reduced 12-month overall survival, increased NRM, and reduced survival in recipients with AGVHD. Assessing IFN-γ response to PHA post-HSCT may be a clinically useful immune biomarker.

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Section: Discussionmentioning

confidence: 96%

Low T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2017

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“…Previous clinical studies of the functional immune reconstitution at different timepoints after HCT have investigated (a) the reactivity of CD4+ T cells based on the amount of adenosine phosphate secreted upon phytohemagglutinin stimulation [21][22][23][24] ; (b) the virus-specific reactivity of CD8+ T cells based on the release of interferon-γ upon stimulation with viral antigens [25][26][27][28][29][30] ; (c) the pathogen-specific proliferative and cytokine responses of peripheral blood mononuclear cells after culturing 31 ; or (d) the phagocytic, migratory and stimulusspecific oxidative capacity of neutrophils and monocytes 32,33 ; among other approaches. While these approaches-to evaluate the post-HCT functional immune reconstitution-are valuable when investigating pathogen-or immune cell-specific responses, our study demonstrates the feasibility of obtaining a more global screening of the circulating immune cells post-HCT, revealing a broad array of cytokine responses elicited through multiple immunologic signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre‐ and post‐transplantation cytokine responses in stimulated whole blood

et al. 2021

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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.

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“…Patients in immunosuppressed states often show a slow decline in viral load, possibly due to a delayed and inadequate T-cell immune response [17,26,27] . We measured ATP CD4 and ATP CD8 , previously confirmed as predictive indicators for disease relapse and poor prognosis in malignancies [28][29][30] , to assess patients' cellular immune responses. Both ATP CD4 and ATP CD8 were significantly reduced in patients with malignancies, even though lymphocyte counts were similar in both the study and control groups.…”

Section: Discussionmentioning

confidence: 99%

Impaired T-cell Reactivity in Hematological Malignancy Patients: Insights into SARS-CoV-2 Omicron Infection and Clinical Implications

2024

FMSR

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The SARS-CoV-2 Omicron variant has posed global health challenges, particularly for individuals with haematological malignancies. This study aimed to characterize clinical and immunological aspects of Omicron-infected haematological malignancy patients and compare them to the general population. In a retrospective study from Dec 3, 2022, to Apr 30, 2023, we assessed SARS-CoV-2-positive patients in the Haematology Department (study group) and randomly selected control patients from other departments. Clinical symptoms were similar, but pneumonia was more common in the patients with haematological malignancies. Haemoglobin and platelet levels were notably lower in the study group, and they had a higher viral load with lower intracellular ATP levels in CD4+ and CD8+ T cells. CD8+ ATP levels were further reduced in lymphocytic malignancies. Risk factors for mortality included age >60 years, ECOG score >3, CRP >50 mg/L, and NLR ≥6.5. This study emphasizes the significance of cellular immune responses in Omicron-infected haematological malignancy patients. Tailored clinical strategies and close monitoring are crucial for this vulnerable group due to potential immune impairments and associated risks.

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CD4 T-cell function assay using Cylex ImmuKnow and lymphocyte subset recovery following allogeneic hematopoietic stem cell transplantation

Cited by 6 publications

References 21 publications

Low T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Low T-Cell Responses to Mitogen Stimulation Predicts Poor Survival in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Functional immune reconstitution early after allogeneic haematopoietic cell transplantation: A comparison of pre‐ and post‐transplantation cytokine responses in stimulated whole blood

Impaired T-cell Reactivity in Hematological Malignancy Patients: Insights into SARS-CoV-2 Omicron Infection and Clinical Implications

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