Anti-CMV Cellular Immunity Quantification Using an IGRA Test in Kidney Transplant récipients and Hemodialysis Patients, Comparison to Control Patients (Quantiferon)
Quantification de l'immunité T Anti-CMV à l'Aide d'un Test IGRA Chez Des Patients greffés rénaux et Des Patients dialysés, Comparaison Avec Une Population de témoins
Study Overview
Status
Intervention / Treatment
Detailed Description
Cytomegalovirus (CMV) infection is a common opportunistic complication after kidney transplantation (KT). It has been associated with high morbidity and mortality in kidney transplant recipients (KTR). Its actual management is only based on the humoral immunity : the main risk factor for CMV infection after KT is the association of a seropositive donor and a seronegative recipient (so-called "D+/R- mismatch").
However several studies have highlighted the essential role of cellular immunity to control CMV infection. The Quantiferon-CMV (QF-CMV) is an IGRA test (Interferon Gamma Releasing Assay) which evaluates T CD8 lymphocytes production of Interferon Gamma (IFNy) exposed to CMV antigens. Some studies have shown the possible interest of the QF-CMV in predicting CMV infection after antiviral prophylaxis discontinuation or when CMV viremia is detected.
However some limits have been underlined. First its positivity threshold hasn't been approved in KTR. Hemodialysis patients (HP) called to receive a renal allograft also suffered from altered immunity. No study has directly compared the QF-CMV value in KTR, HP and control patients.
That's why we propose evaluating the expression of basal cellular immunity against CMV (far from any active infection) in KTR and HP using the QF-CMV and comparing it to control patients population (not suffering from kidney dysfunction or immunosuppression).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Grenoble, France, 38043
- CHU Grenoble Alpes
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Kidney transplant recipients will be recruited among KTR followed in the Kidney transplant department of Grenoble University Hospital.
Hemodialysis patients will be recruited among hemodialysis patients on the waiting list for a kidney transplant in the Kidney transplant department of Grenoble University Hospital.
Control patients will be recruited among non-hemodialysis and non-kidney transplanted patients followed in the Grenoble University Hospital.
Description
Inclusion Criteria :
For all patients :
- to be seropositive for CMV
- to not be opposed to the study
For kidney transplant recipients :
- to have received a kidney graft for over 1 year
- to have received an induction therapy at transplantation time by anti-lymphocytes antibodies and steroids
- to be currently receiving immunosuppressive therapy by calcineurins inhibitors (tacrolimus or cyclosporine), mycophenolic acid with or without steroids
- to not suffer from another cause of immunosuppression
For hemodialysis patients :
- to be treated by hemodialysis for end stage renal disease
- without prior solid organ transplant history
- to not suffer from another cause of immunosuppression
For control patients :
- with normal kidney function (estimated GFR > 90 ml/min)
- to not suffer from another cause of immunosuppression
Exclusion Criteria :
- patient under guardianship or deprived of his liberty
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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Group 1 : kidney transplant recipients (KTR)
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Evaluate and compare interferon gamma (IFNy) production by T CD8 cells exposed to CMV antigens in CMV seropositive kidney transplant recipients, hemodialysis and control patients
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Group 2 : hemodialysis patients
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Evaluate and compare interferon gamma (IFNy) production by T CD8 cells exposed to CMV antigens in CMV seropositive kidney transplant recipients, hemodialysis and control patients
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Group 3 : Control patients
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Evaluate and compare interferon gamma (IFNy) production by T CD8 cells exposed to CMV antigens in CMV seropositive kidney transplant recipients, hemodialysis and control patients
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Quantification of anti-CMV T cellular immunity in kidney transplant recipients, hemodialysis patients and control patients.
Time Frame: Single measurement at Day 0 of patient inclusion
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Quantification of IFNy level producted by T cells exposed to CMV antigens using a Quantiferon-CMV test in kidney transplant recipients, hemodialysis patients and control patients.
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Single measurement at Day 0 of patient inclusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Quantification of patient cellular immunity.
Time Frame: Single measurement at Day 0 of patient inclusion
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Quantification of lymphocytes subpopulations.
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Single measurement at Day 0 of patient inclusion
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Evaluation of kidney transplant recipient exposure to immunosuppressive therapy.
Time Frame: Single collection at Day 0 of patient inclusion
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Assessment of last tacrolimus trough concentration.
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Single collection at Day 0 of patient inclusion
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Estimation of renal function.
Time Frame: Single measurement at Day 0 of patient inclusion
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Evaluation of estimated glomerular filtration rate by plasmatic creatinin dosage using CKD-EPI estimate.
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Single measurement at Day 0 of patient inclusion
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Assessment of CMV donor humoral immunity in kidney transplant recipients.
Time Frame: Single collection at Day 0 of patient inclusion
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Assessment of donor CMV serology.
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Single collection at Day 0 of patient inclusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lionel Rostaing, Centre Hospitalier Universitaire Grenoble-Alpes
Publications and helpful links
General Publications
- Radha R, Jordan S, Puliyanda D, Bunnapradist S, Petrosyan A, Amet N, Toyoda M. Cellular immune responses to cytomegalovirus in renal transplant recipients. Am J Transplant. 2005 Jan;5(1):110-7. doi: 10.1111/j.1600-6143.2003.00647.x.
- Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation. 2012 Jan 27;93(2):195-200. doi: 10.1097/TP.0b013e31823c1cd4.
- Kumar D, Chernenko S, Moussa G, Cobos I, Manuel O, Preiksaitis J, Venkataraman S, Humar A. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am J Transplant. 2009 May;9(5):1214-22. doi: 10.1111/j.1600-6143.2009.02618.x.
- Manuel O, Husain S, Kumar D, Zayas C, Mawhorter S, Levi ME, Kalpoe J, Lisboa L, Ely L, Kaul DR, Schwartz BS, Morris MI, Ison MG, Yen-Lieberman B, Sebastian A, Assi M, Humar A. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24. doi: 10.1093/cid/cis993. Epub 2012 Nov 29.
- Cantisan S, Lara R, Montejo M, Redel J, Rodriguez-Benot A, Gutierrez-Aroca J, Gonzalez-Padilla M, Bueno L, Rivero A, Solana R, Torre-Cisneros J. Pretransplant interferon-gamma secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant. 2013 Mar;13(3):738-45. doi: 10.1111/ajt.12049. Epub 2013 Jan 11.
- Walker S, Fazou C, Crough T, Holdsworth R, Kiely P, Veale M, Bell S, Gailbraith A, McNeil K, Jones S, Khanna R. Ex vivo monitoring of human cytomegalovirus-specific CD8+ T-cell responses using QuantiFERON-CMV. Transpl Infect Dis. 2007 Jun;9(2):165-70. doi: 10.1111/j.1399-3062.2006.00199.x.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 38RC19.002
- 2019-A00101-56 (Other Identifier: ID RCB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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