Assessment of CD4 T-lymphocyte reactivity by the Cylex ImmuKnow assay in patients following allogeneic hematopoietic SCT

Gesundheit, Benjamin; Budowski, Einat; Israeli, Moshe; Shapira, Michael Y.; Resnick, Igor B.; Bringer, Rachel; Azar, Yehudith; Samuel, Simcha; Dray, L; Amar, A.; Kristt, Donald A.; Or, Reuven

doi:10.1038/bmt.2009.182

Cited by 15 publications

(8 citation statements)

References 23 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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“…In addition, results cannot be extrapolated to haploidentical and cord blood patients as, at the time of performance of the study, there were few such donors utilized at our center. Assessing what impact these alternative donors have on the QFM assay would be important, given the different immune recovery profiles of these alternative transplants . Finally, immune function in later phases of an alloHCT has not been explored in this study; however, a cross‐sectional study assessing IFN‐γ levels in QFM assay at later time points post‐transplant is currently underway at our center.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, tests that assess immune reconstitution and hence risk of infection consist primarily of lymphocyte subset analyses and immunoglobulin levels. These are not functional tests and may not accurately measure immune recovery . There is therefore an unmet need for a non‐invasive, simple test to help predict or detect the early development of infection and GVHD and help titrate the immunosuppression required to avoid toxicities and infections.…”

Section: Introductionmentioning

confidence: 99%

The QuantiFERON Monitor^® assay is predictive of infection post allogeneic hematopoietic cell transplantation

Douglas

Sundararajan

et al. 2020

Transplant Infectious Dis

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Introduction Following allogeneic hematopoietic stem cell transplantation (alloHCT), excessive immunosuppression can be complicated by infection, while inadequate immunosuppression can result in graft‐vs‐host disease (GVHD). An accurate method to assess overall immune status post HCT is lacking. The QuantiFERON Monitor® (QFM) assay measures interferon gamma (IFN‐γ) release from whole blood following incubation with both innate (Toll‐like receptor 7, TLR7) and adaptive (CD3 antibody) stimulants and may result in a more complete assessment of the immune system. Methods Whole blood samples were prospectively collected from alloHCT recipients at conditioning followed by days 10, 30, 60, 90, 120, and 180 post‐transplant and assayed by the QFM test. IFN‐γ levels were correlated to time post HCT and episodes of infection and GVHD. Results Forty patients were enrolled in the study (68% male; median age 47 years; 58% matched related donors, 42% unrelated; 33% myeloablative). Post‐stimulation IFN‐γ levels rose steadily over the first 180 days post transplantation. IFN‐γ levels were significantly lower in those with active infection compared to those without during the neutropenic period (P < .001). The assay was predictive of CMV reactivation (VL > 1000 copies/mL) post alloHCT (P = .001). Conclusion This is a promising assay to demonstrate immune recovery and predict risk of infection after alloHCT and may allow tailoring of immunosuppression, antimicrobial treatment, and prophylaxis.

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“… studied its relevance in the context of autologous HCT and is therefore not instructive for our study of patients going through allogeneic HCT. Thus far, only one publication has described utilization of the ImmuKnow assay for immune monitoring post‐allogeneic HCT . However, there are several apparent differences between the latter and the current study.…”

Section: Discussionmentioning

confidence: 79%

Cellular immune function monitoring after allogeneic haematopoietic cell transplantation: evaluation of a new assay

Israeli

Klein

Herscovici

et al. 2013

Clinical and Experimental Immunology

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SummaryManaging the patient's immune system after haematopoietic cell transplantation (HCT) is a challenge, mainly in the unstable period immediately after the transplant. Currently there is no standardized non-invasive diagnostic tool for the evaluation of immunological complications such as graft-versushost disease (GVHD) and for managing the cellular immune function of the transplant recipient. The ImmuKnow assay for cellular immune function monitoring has been incorporated successfully into the clinical follow-up routine of solid organ transplant recipients. This study aims to explore the relevance and potential contribution of immune monitoring using the assay in the setting of HCT. We found that ImmuKnow-level measurement can distinguish between states of immune function quiescence and between events of acute GVHD. ImmuKnow levels were significantly higher in patients going through GVHD than the levels measured for the same patients during immunological stability. Moreover, we demonstrate a patient case where longitudinal monitoring using the ImmuKnow assay provided a trustworthy depiction of the patient's cellular immune function post-HCT. In conclusion, we provide evidence for the potential contribution of the ImmuKnow assay for longitudinal individualized cellular immune function monitoring of patients following HCT. Further studies are necessary in order to establish the optimal practice for utilizing the assay for this purpose.

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Assessment of CD4 T-lymphocyte reactivity by the Cylex ImmuKnow assay in patients following allogeneic hematopoietic SCT

Cited by 15 publications

References 23 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

The QuantiFERON Monitor^® assay is predictive of infection post allogeneic hematopoietic cell transplantation

Cellular immune function monitoring after allogeneic haematopoietic cell transplantation: evaluation of a new assay

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Assessment of CD4 T-lymphocyte reactivity by the Cylex ImmuKnow assay in patients following allogeneic hematopoietic SCT

Cited by 15 publications

References 23 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

The QuantiFERON Monitor® assay is predictive of infection post allogeneic hematopoietic cell transplantation

Cellular immune function monitoring after allogeneic haematopoietic cell transplantation: evaluation of a new assay

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The QuantiFERON Monitor^® assay is predictive of infection post allogeneic hematopoietic cell transplantation