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Diagnostic usefulness of the cytomegalovirus (CMV)-specific T cell-based assay for predicting CMV infection after kidney transplant

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Background/Aims: We evaluated the usefulness in kidney transplant (KT) candidates of cytomegalovirus (CMV)-specific enzyme-linked immunospot (ELISPOT) assays for predicting the development of post-transplant CMV infections. Methods: All adult recipients admitted for living-donor KT between March 2014 and March 2015 were prospectively enrolled except donor CMV-seropositive and recipient seronegative (D+/R–) recipients. All the enrolled patients underwent CMV-specific ELISPOT assays before transplant, and a researcher blinded to the results of these assays examined the patients for CMV infection at least 6 months post-transplant. Results: Of 133 KT recipients, 44 (33%) developed CMV infections. When we used the cut-off determined by receiver operator characteristic curve, 16 of the 34 patients (47%) with negative pp65-specific ELISPOT results (< 11 spots/200,000 cells) developed CMV infections, whereas 28 of the 99 patients (39%) with positive pp65-specific ELISPOT results at baseline (≥ 11 spots/200,000 cells) developed CMV infections after KT (p = 0.02). Based on the multivariable Cox regression model, negative pp65-specific ELISPOT assay results was an independent risk factor for CMV infection (adjusted hazard ratio [AHR], 1.87; 95% confidence interval [CI], 1.01 to 3.46; p = 0.047) as well as age (AHR, 1.05; 95% CI, 1.01 to 1.08; p = 0.007). Conclusions: Pre-transplant CMV-specific ELISPOT assay appears to predict the development of CMV infections after KT in recipients at moderate risk such as CMV-seropositive recipients (Clinical Trial Registration Number NCT 02025335).

Abstract

Background/Aims: We evaluated the usefulness in kidney transplant (KT) candidates of cytomegalovirus (CMV)-specific enzyme-linked immunospot (ELISPOT) assays for predicting the development of post-transplant CMV infections. Methods: All adult recipients admitted for living-donor KT between March 2014 and March 2015 were prospectively enrolled except donor CMV-seropositive and recipient seronegative (D+/R–) recipients. All the enrolled patients underwent CMV-specific ELISPOT assays before transplant, and a researcher blinded to the results of these assays examined the patients for CMV infection at least 6 months post-transplant. Results: Of 133 KT recipients, 44 (33%) developed CMV infections. When we used the cut-off determined by receiver operator characteristic curve, 16 of the 34 patients (47%) with negative pp65-specific ELISPOT results (< 11 spots/200,000 cells) developed CMV infections, whereas 28 of the 99 patients (39%) with positive pp65-specific ELISPOT results at baseline (≥ 11 spots/200,000 cells) developed CMV infections after KT (p = 0.02). Based on the multivariable Cox regression model, negative pp65-specific ELISPOT assay results was an independent risk factor for CMV infection (adjusted hazard ratio [AHR], 1.87; 95% confidence interval [CI], 1.01 to 3.46; p = 0.047) as well as age (AHR, 1.05; 95% CI, 1.01 to 1.08; p = 0.007). Conclusions: Pre-transplant CMV-specific ELISPOT assay appears to predict the development of CMV infections after KT in recipients at moderate risk such as CMV-seropositive recipients (Clinical Trial Registration Number NCT 02025335).

참고문헌 (51)

  1. Fishman JA, "Infection in solid-organ transplant recipients", N Engl J Med, 357, pp.2601~2614 (2007)
  2. Razonable RR, "Cytomegalovirus in solid organ transplantation", Am J Transplant, 13(Suppl 4), pp.93~106 (2013)
  3. Fishman JA, "Cytomegalovirus in transplantation : challenging the status quo", Clin Transplant, 21, pp.149~158 (2007)
  4. Hahn JS, "A survey on the cytomegalovirus antibodies in blood donors and the diseased", Korean J Blood Transfus, 1, pp.21~33 (1990)
  5. Barron MA, "Relationship of reconstituted adaptive and innate cytomegalovirus (CMV)-specific immune responses with CMV viremia in hematopoietic stem cell transplant recipients", Clin Infect Dis, 49, pp.1777~1783 (2009)
  6. Egli A, "State-of-the-art monitoring of cytomegalovirus-specific cell-mediated immunity after organ transplant: a primer for the clinician", Clin Infect Dis, 55, pp.1678~1689 (2012)
  7. Mori T, "Risk-adapted pre-emptive therapy for cytomegalovirus disease in patients undergoing allogeneic bone marrow transplantation", Bone Marrow Transplant, 25, pp.765~769 (2000)
  8. Ljungman P, "Definitions of cytomegalovirus infection and disease in transplant recipients", Clin Infect Dis, 34, pp.1094~1097 (2002)
  9. 김성한, "Diagnostic Usefulness of Cytomegalovirus (CMV)- Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of- Concept Study", Infection and Chemotherapy, 47(2), pp.105~110 (2015), 대한감염학회[DOI]
  10. Kim SH, "Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells", Clin Infect Dis, 50, pp.1349~1358 (2010)
  11. Tark Kim, "Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy", The Korean Journal of Internal Medicine, 31(5), pp.961~970 (2016), 대한내과학회[DOI]
  12. Crough T, "Immunobiology of human cytomegalovirus : from bench to bedside", Clin Microbiol Rev, 22, pp.76~98 (2009)
  13. Sund F, "CMV-specific T-cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients : a pilot study", Clin Transplant, 24, pp.401~409 (2010)
  14. Ravkov EV, "Validation of cytomegalovirus immune competence assays for the characterization of CD8(+) T cell responses posttransplant", Clin Dev Immunol, 2012, pp.451059~ (2012)
  15. Ritter M, "Cytomegalovirus-specific T cells are detectable in early childhood and allow assignment of the infection status in children with passive maternal antibodies", Eur J Immunol, 43, pp.1099~1108 (2013)
  16. Sester U, "PD-1 expression and IL-2 loss of cytomegalovirusspecific T cells correlates with viremia and reversible functional anergy", Am J Transplant, 8, pp.1486~1497 (2008)
  17. Bunde T, "Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells", J Exp Med, 201, pp.1031~1036 (2005)
  18. Sester U, "Differences in CMV-specific T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation", Am J Transplant, 5, pp.1483~1489 (2005)
  19. Sester M, "Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation", Transplantation, 71, pp.1287~1294 (2001)
  20. Egli A, "Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients", J Transl Med, 6, pp.29~ (2008)
  21. Gerna G, "Virologic and immunologic monitoring of cytomegalovirus to guide preemptive therapy in solid-organ transplantation", Am J Transplant, 11, pp.2463~2471 (2011)
  22. Pipeling MR, "Primary cytomegalovirus phosphoprotein 65-specific CD8+ T-cell responses and T-bet levels predict immune control during early chronic infection in lung transplant recipients", J Infect Dis, 204, pp.1663~1671 (2011)
  23. Gabanti E, "Human cytomegalovirus(HCMV)-specific CD4+ and CD8+ T cells are both required for prevention of HCMV disease in seropositive solid-organ transplant recipients", PLoS One, 9, pp.e106044~ (2014)
  24. Snyder LD, "Polyfunctional T-cell signatures to predict protection from cytomegalovirus after lung transplantation", Am J Respir Crit Care Med, 193, pp.78~85 (2016)
  25. Eid AJ, "A prospective longitudinal analysis of cytomegalovirus (CMV)-specific CD4+and CD8+ T cells in kidney allograft recipients at risk of CMV infection", Transpl Int, 23, pp.506~513 (2010)
  26. Abate D, "Evaluation of cytomegalovirus (CMV)-specific T cell immune reconstitution revealed that baseline antiviral immunity, prophylaxis, or preemptive therapy but not antithymocyte globulin treatment contribute to CMV-specific T cell reconstitution in kidney transplant recipients", J Infect Dis, 202, pp.585~594 (2010)
  27. Abate D, "Human cytomegalovirus-specific T-cell immune reconstitution in preemptively treated heart transplant recipients identifies subjects at critical risk for infection", J Clin Microbiol, 50, pp.1974~1980 (2012)
  28. Abate D, "Comparison of cytomegalovirus (CMV) enzyme-linked immunosorbent spot and CMV quantiferon gamma interferon-releasing assays in assessing risk of CMV infection in kidney transplant recipients", J Clin Microbiol, 51, pp.2501~2507 (2013)
  29. Kumar D, "Cell-mediated immunity to predict cytomegalovirus disease in highrisk solid organ transplant recipients", Am J Transplant, 9, pp.1214~1222 (2009)
  30. Lisboa LF, "Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia", Transplantation, 93, pp.195~200 (2012)
  31. Clari MA, "Performance of the QuantiFERON-cytomegalovirus (CMV) assay for detection and estimation of the magnitude and functionality of the CMV-specific gamma interferon-producing CD8(+) T-cell response in allogeneic stem cell transplant recipients", Clin Vaccine Immunol, 19, pp.791~796 (2012)
  32. Manuel O, "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, 56, pp.817~824 (2013)
  33. Westall GP, "Linking CMV serostatus to episodes of CMV reactivation following lung transplantation by measuring CMV-specific CD8+ T-cell immunity", Am J Transplant, 8, pp.1749~1754 (2008)
  34. Lochmanova A, "Quantiferon-CMV test in prediction of cytomegalovirus infection after kidney transplantation", Transplant Proc, 42, pp.3574~3577 (2010)
  35. Weseslindtner L, "Prospective analysis of human cytomegalovirus DNAemia and specific CD8+ T cell responses in lung transplant recipients", Am J Transplant, 12, pp.2172~2180 (2012)
  36. Cantisan S, "Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation", Am J Transplant, 13, pp.738~745 (2013)
  37. Hong SI, "Is the sensitivity of the QuantiFERON-TB gold in-tube test lower than that of T-SPOT.TB in patients with military tuberculosis?", Clin Infect Dis, 59, pp.142~ (2014)
  38. Chiereghin A, "Monitoring cytomegalovirus T-cell immunity in small bowel", multivisceral transplant recipients, 2010, pp.42, 69~73
  39. Costa C, "Evaluation and significance of cytomegalovirus-specific cellular immune response in lung transplant recipients", Transplant Proc, 43, pp.1159~1161 (2011)
  40. Patel M, "Dynamics of cell-mediated immune responses to cytomegalovirus in pediatric transplantation recipients", Pediatr Transplant, 16, pp.18~28 (2012)
  41. Bestard O, "Pretransplant immediately early-1-specific T cell responses provide protection for CMV infection after kidney transplantation", Am J Transplant, 13, pp.1793~1805 (2013)
  42. Costa C, "Evaluation of CMV-specific cellular immune response by EliSPOT assay in kidney transplant patients", J Clin Virol, 61, pp.523~528 (2014)
  43. Ritta M, "Pre-transplant assessment of CMV-specific immune response by Elispot assay in kidney transplant recipients", New Microbiol, 38, pp.329~335 (2015)
  44. Nikolich-Zugich J, "Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections", Nat Rev Immunol, 8, pp.512~522 (2008)
  45. Galiatsatos P, "Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts", Dig Dis Sci, 50, pp.609~616 (2005)
  46. Bernard S, "Symptomatic cytomegalovirus gastrointestinal infection with positive quantitative real-time PCR findings in apparently immunocompetent patients : a case series", Clin Microbiol Infect, 21, pp.1121~ (2015)
  47. Schachtner T, "The loss of BKV-specific immunity from pretransplantation to posttransplantation identifies kidney transplant recipients at increased risk of BKV replication", Am J Transplant, 15, pp.2159~2169 (2015)
  48. Kim JW, "Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide-based chemotherapy", J Clin Virol, 73, pp.64~69 (2015)
  49. Boeckh M, "Quantitation of cytomegalovirus : methodologic aspects and clinical applications", Clin Microbiol Rev, 11, pp.533~554 (1998)
  50. Moon SM, "Diagnostic yield of the cytomegalovirus (CMV) antigenemia assay and clinical features in solid organ transplant recipients and hematopoietic stem cell transplant recipients with CMV pneumonia", Transpl Infect Dis, 14, pp.192~197 (2012)
  51. Cariani E, "Relationship between pp65 antigenemia levels and real-time quantitative DNA PCR for human cytomegalovirus (HCMV) management in immunocompromised patients", BMC Infect Dis, 7, pp.138~ (2007)

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