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

Abstract

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.

Development of a Simple and Robust Whole Blood Assay with Dual Co-Stimulation to Quantify the Release of T-Cellular Signature Cytokines in Response to Aspergillus fumigatus Antigens

“…There is increasing interest in WB-based profiling of adaptive immune responses in infectious diseases and, to that end, a number of investigational and commercial assay systems have been developed [17,46]. WB assays for the detection of antigen-reactive T-cells have several important advantages over their PBMC-based counterparts as they require less blood volume and hands-on-time, facilitate improved standardization, and are often more cost-efficient [47][48][49].…”

“…To overcome these drawbacks, there is a growing interest in the development of whole blood (WB)-based protocols to determine T-cell responses to fungal antigens [15,16], following the clinical success of WB-based tests in tuberculosis and cytomegalovirus (CMV) diagnostics and research [17][18][19]. Although WB assays are more robust than PBMCbased protocols [16], concerns about impaired test performance remain when stimulation conditions are suboptimal, e.g., in the presence of immunosuppressive therapy or after long pre-analytic delays [16,[20][21][22][23].…”

Evaluation of Quantiferon®‐Monitor as a biomarker of immunosuppression and predictor of infection in lung transplant recipients

“…In fact the QFM levels seen in our cohort were more similar to bone marrow transplant recipients. 12 The ImmuKnow® assay (Cylex/Viracor-Eurofins, USA) is a widely studied immune biomarker that measures adenosine triphosphate (ATP) release from CD4+ T-lymphocytes after phytohemagglutinin-L (PHA) stimulation, which is thought to represent T-cell function. 4,21,22 Despite being FDA approved in 2002, there has not been widespread clinical uptake in this test mainly due to difficulties in defining cutoffs…”

“…11 More recently, QFM has been evaluated in bone marrow transplant recipients and low levels were associated with infections during the pre-engraftment period. 12 An improved ability to measure net state of immunosuppression would allow for individualization of immunosuppressive therapy before clinical events occur, potentially minimizing the risk of both under-immunosuppression leading to rejection and over-immunosuppression resulting in infection and drug toxicity. The aims of this study were to evaluate QFM both as a biomarker of immunosuppression and as a tool for the prediction of infection and rejection in a prospective observational cohort of lung transplant recipients (LTR).…”

ELISPOT assay of interferon‐γ secretion for evaluating human cytomegalovirus reactivation risk in allo‐HSCT recipients

“…8,35 Recent studies reported that the ELISPOT assay for IFN-γ secretion of HCMV-specific CD8 + T cells performed well at predicting recurrent HCMV reactivation. 6,36 The HCMV serostatus of the patient and donor is one of the most important variables influencing HCMV-specific T cell immune reconstitution. 37,38 HCMV-seropositive recipients and donors (R + D + ) have a much faster reconstitution of HCMV-specific CD8 + T cells than HCMV-seropositive recipients transplanted from HCMVseronegative donors (R + D − ).…”