QuantiFERON-CMV (QF-CMV) is an in vitro assay using a peptide cocktail simulating human cytomegalovirus (CMV) proteins to stimulate cells in heparinized whole blood. Detection of interferon gamma (IFN-) by Enzyme-linked immunosorbent Assay (ELISA) is used to quantify in vitro responses to these peptide antigens that are associated with immune control of CMV infection. Loss of this immune function may be associated with development of CMV disease. The intended use of QF-CMV is to monitor a patient’s level of anti-CMV immunity. QF-CMV is not a test for determining CMV infection and should not be used to exclude CMV infection. Immune monitoring of CMV-specific T cell responses may predict individuals at risk of CMV disease post transplant and may be useful in guiding prophylaxis and pre-emptive therapies. CMV is a herpes virus that infects between 50 – 85% of adults. Primary infection is followed by life long latency. It is particularly problematic in immunosuppressed patients post transplant, contributing to morbidity and mortality. Current immunosuppressive therapies used to prevent the rejection of a transplanted organ have a detrimental effect on T cells and cell mediated immunity (CMI), resulting in increased susceptibility to viral infections post-transplant. CD8+ cytotoxic T cell (CTL) can protect against virus-associated pathogenesis. Enumeration of CMV-specific CTL in immunosuppressed patients requires knowledge of patient HLA type and tetramer availability, and is prohibitively expensive for routine monitoring purposes. IFN- production is a functional surrogate for the identification of CMV-specific CTLs. Thus the production of IFN-may be predictive of the risk of developing CMV disease. Interferon gamma release assays (IGRAs) such as QF-CMV are simple to perform, cost effective, reproducible and have rapid turnaround times. It is currently the only standardized commercial immune monitoring assay capable of detecting CMV-induced IFN-. QF-CMV is an assay for CMI responses to CMV peptide antigens. The CMV peptides are designed to target CD8+ T cells, including A1, A2, A3, A11, A23, A24, A26, B7, B8, B27, B35, B40, B41, B44, B51, B52, B57, B58, B60 and Cw6 (A30, B13) HLA Class I haplotypes, covering >98% of the human population. Individuals infected with CMV usually have CD8+ T cells in their blood that recognize these antigens. This recognition process involves the generation and secretion of the cytokine IFN-. The detection and quantitation of IFN- forms the basis of this test.
No specific patient preparation required
Use of QF-CMV in solid organ transplantation. CMV serology is widely used pre-transplantation to establish risk of CMV complications post transplantation, but has limited value post-transplantation. QF-CMV may be used to assess CMV immunity post transplantation, in patients at risk of developing symptomatic CMV disease due to immunosuppression. • Transplant patients with QF-CMV Reactive result at completion of anti-CMV prophylaxis have a significantly lower rate of late onset disease compared with those having a QF-CMV Non-Reactive result. • Higher risk transplant patients (ie CMV+/CMV-) with a Reactive QF-CMV result any time post prophylaxis have a 90% chance of remaining free from CMV disease. • QF-CMV may prove useful in the prediction of spontaneous viral clearance compared to CMV disease progression following elevations in CMV viraemia. Higher incidence of post transplant CMV replication was seen in recipients with a QF-CMV Non-Reactive result compared to recipients with a Reactive result. • Pre-transplant QF-CMV Non-Reactive recipients who receive an organ from a CMV-seropositive donor have a 10-fold increase of CMV replication compared to a pre-transplant QF-CMT Reactive recipient. Use of QF-CMV in haematological transplantation. In haemopoietic stem cell transplantation (HSCT), reactivation of latent virus is more common than acquisition of primary infection. Preventing reactivation required a robust T cell mediated immune reponse. Immunosuppression and T cell depleting protocols used pre-HSCT affect the risk of reactivation. Delayed reconstitution of cellular immunity and cytopenias, as well as toxicity of anti-viral drugs (particularly ganciclovir) post-HSCT, is particularly problematic. HLA-mis matched transplants where immunosuppression is increased and GVHD more likely, are particularly likely to reactivate CMV, and have a survival disadvantage. Pre-transplant screening and pre-emptive therapy based on CMV viral load are employed routinely by transplant centres. Demonstration of a CMV-specific T cell response may help: • select patients who do not require continual treatment • assist therapeutic decisions regarding anti-viral drug use (reducing unnecessary drug toxicities and myelosuppressive side effects) and donor T cell infusions.
Results reported as interpretive comments: Anti CMV immunity NOT detected Anti-CMV immunity detected Result indeterminate for CMV responsiveness
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Tests not appearing on this scope are either under consideration or in the process of accreditation and so currently remain outside of our scope of accreditation. However, these tests have been validated to the same high standard as accredited tests and are performed by the same trained and competent staff.
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