DOI QR코드

DOI QR Code

Comparison of Quantitation of Cytomegalovirus DNA by Real-Time PCR in Whole Blood with the Cytomegalovirus Antigenemia Assay

  • Kwon, Seonhee (Department of Laboratory Medicine, College of Medicine, Korea University) ;
  • Jung, Bo Kyeung (Department of Laboratory Medicine, College of Medicine, Korea University) ;
  • Ko, Sun-Young (Department of Laboratory Medicine, College of Medicine, Korea University) ;
  • Lee, Chang Kyu (Department of Laboratory Medicine, College of Medicine, Korea University) ;
  • Cho, Yunjung (Department of Laboratory Medicine, College of Medicine, Korea University)
  • Received : 2014.08.05
  • Accepted : 2014.10.19
  • Published : 2015.01.02

Abstract

Background: Quantitation of cytomegalovirus (CMV) DNA using real-time PCR has been utilized for monitoring CMV infection. However, the CMV antigenemia assay is still the 'gold standard' assay. There are only a few studies in Korea that compared the efficacy of use of real-time PCR for quantitation of CMV DNA in whole blood with the antigenemia assay, and most of these studies have been limited to transplant recipients. Method: 479 whole blood samples from 79 patients, falling under different disease groups, were tested by real-time CMV DNA PCR using the Q-CMV real-time complete kit (Nanogen Advanced Diagnostic S.r.L., Italy) and CMV antigenemia assay (CINA Kit, ArgeneBiosoft, France), and the results were compared. Repeatedly tested patients were selected and their charts were reviewed for ganciclovir therapy. Results: The concordance rate of the two assays was 86.4% (Cohen's kappa coefficient value=0.659). Quantitative correlation between the two assays was a moderate (r=0.5504, P<0.0001). Among 20 patients tested repeatedly with the two assays, 13 patients were transplant recipients and treated with ganciclovir. Before treatment, CMV was detected earlier by real-time CMV DNA PCR than the antigenemia assay, with a median difference of 8 days. After treatment, the antigenemia assay achieved negative results earlier than real-time CMV DNA PCR with a median difference of 10.5 days. Conclusions: Q-CMV real-time complete kit is a useful tool for early detection of CMV infection in whole blood samples in transplant recipients.

Keywords

References

  1. Paya CV. Prevention of cytomegalovirus disease in recipients of solid-organ transplants. Clin Infect Dis 2001;32:596-603. https://doi.org/10.1086/318724
  2. Boeckh M and Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 1998;11:533-54.
  3. Allice T, Cerutti F, Pittaluga F, Varetto S, Franchello A, Salizzoni M, et al. Evaluation of a novel real-time PCR system for cytomegalovirus DNA quantitation on whole blood and correlation with pp65-antigen test in guiding pre-emptive antiviral treatment. J Virol Methods 2008;148:9-16. https://doi.org/10.1016/j.jviromet.2007.10.006
  4. Guiver M, Fox AJ, Mutton K, Mogulkoc N, Egan J. Evaluation of CMV viral load using TaqMan CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients. Transplantation 2001;71:1609-15. https://doi.org/10.1097/00007890-200106150-00021
  5. Camargo LF, Uip DE, Simpson AA, Caballero O, Stolf NA, Vilas-Boas LS, et al. Comparison between antigenemia and a quantitative-competitive polymerase chain reaction for the diagnosis of cytomegalovirus infection after heart transplantation. Transplantation 2001;71:412-7. https://doi.org/10.1097/00007890-200102150-00013
  6. Heid CA, Stevens J, Livak KJ, Williams PM. Realtime quantitative PCR. Genome Res 1996;6:986-94. https://doi.org/10.1101/gr.6.10.986
  7. Choi SM, Lee DG, Lim J, Park SH, Choi JH, Yoo JH, et al. Comparison of quantitative cytomegalovirus real-time PCR in whole blood and pp65 antigenemia assay: clinical utility of CMV real-time PCR in hematopoietic stem cell transplant recipients. J Korean Med Sci 2009;24:571-8. https://doi.org/10.3346/jkms.2009.24.4.571
  8. Marchetti S, Santangelo R, Manzara S, D'onghia S, Fadda G, Cattani P. Comparison of real-time PCR and pp65 antigen assays for monitoring the development of Cytomegalovirus disease in recipients of solid organ and bone marrow transplants. New Microbiol 2011;34:157-64.
  9. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002;34:1094-7. https://doi.org/10.1086/339329
  10. Paya CV, Wilson JA, Espy MJ, Sia IG, DeBernardi MJ, Smith TF, et al. Preemptive use of oral ganciclovir to prevent cytomegalovirus infection in liver transplant patients: a randomized, placebo-controlled trial. J Infect Dis 2002;185:854-60. https://doi.org/10.1086/339449
  11. Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Danziger-Isakov L, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation 2013;96:333-60. https://doi.org/10.1097/TP.0b013e31829df29d
  12. Griffiths PD and Whitley RJ, eds. Recommendations from the International Herpes Management Forum (IHMF) Managements Strategies Workshop and 8th Annual Meeting of the IHMF. The challenge of CMV infection and disease in transplantation.UK: Cambridge Medical Publications, 2000.
  13. Lilleri D, Baldanti F, Gatti M, Rovida F, Dossena L, De Grazia S, et al. Clinically-based determination of safe DNAemia cutoff levels for preemptive therapy or human cytomegalovirus infections in solid organ and hematopoietic stem cell transplant recipients. J Med Virol 2004;73:412-8. https://doi.org/10.1002/jmv.20107
  14. Razonable RR, Brown RA, Wilson J, Groettum C, Kremers W, Espy M, et al. The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation 2002;73:968-73. https://doi.org/10.1097/00007890-200203270-00025
  15. Von Muller L, Hampl W, Hinz J, Meisel H, Reip A, Engelmann E, et al. High variability between results of different in-house tests for cytomegalovirus (CMV) monitoring and a standardized quantitative plasma CMV PCR assay. J Clin Microbiol 2002;40:2285-7. https://doi.org/10.1128/JCM.40.6.2285-2287.2002
  16. Heo WB, Won DI, Kim YL, Kim MH, Oh HB, Suh JS. Evaluation of Biosewoom Real-Q Cytomegalovirus Quantification kit for Cytomegalovirus viral load measure. Korean J Lab Med 2007;27:298-304. https://doi.org/10.3343/kjlm.2007.27.4.298
  17. Li H, Dummer JS, Estes WR, Meng S, Wright PF, Tang YW. Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients. J Clin Microbiol 2003;41:187-91. https://doi.org/10.1128/JCM.41.1.187-191.2003
  18. Kalpoe JS, Kroes AC, de Jong MD, Schinkel J, de Brouwer CS, Beersma MF, et al. Validation of clinical application of cytomegalovirus plasma DNA load measurement and definition of treatment criteria by analysis of correlation to antigen detection. J Clin Microbiol 2004;42:1498-504. https://doi.org/10.1128/JCM.42.4.1498-1504.2004
  19. Mhiri L, Kaabi B, Houimel M, Arrouji Z, Slim A. Comparison of pp65 antigenemia, quantitative PCR and DNA hybrid capture for detection of cytomegalovirus in transplant recipients and AIDS patients. J Virol Methods 2007;143:23-8. https://doi.org/10.1016/j.jviromet.2007.01.033
  20. Ghaffari SH, Obeidi N, Dehghan M, Alimoghaddam K, Gharehbaghian A, Ghavamzadeh A. Monitoring of cytomegalovirus reactivation in bone marrow transplant recipients by real-time PCR. Pathol Oncol Res 2008;14:399-409. https://doi.org/10.1007/s12253-008-9030-3
  21. Pillet S, Roblin X, Cornillon J, Mariat C, Pozzetto B. Quantification of cytomegalovirus viral load. Expert Rev Anti Infect Ther 2014;12:193-210. https://doi.org/10.1586/14787210.2014.870887
  22. Kim DJ, Kim SJ, Park J, Choi GS, Lee S, Kwon CD, et al. Real-time PCR assay compared with antigenemia assay for detecting cytomegalovirus infection in kidney transplant recipients. Transplant Proc 2007;39:1458-60. https://doi.org/10.1016/j.transproceed.2007.01.088
  23. Rhee JY, Peck KR, Lee NY, Song JH. Clinical usefulness of plasma quantitative polymerase chain reaction assay: diagnosis of cytomegalovirus infection in kidney transplant recipients. Transplant Proc 2011;43:2624-9. https://doi.org/10.1016/j.transproceed.2011.05.054

Cited by

  1. Human leukocyte antigen-A genotype as a predictor of cytomegalovirus-pp65 antigenemia and cytomegalovirus disease in solid-organ transplant recipients vol.17, pp.4, 2016, https://doi.org/10.1016/j.ejmhg.2015.12.009
  2. Intestinal perforation due to hemorrhagic Cytomegalovirus enteritis in a patient with severe uncontrolled lupus nephritis: a case and review of the literature vol.37, pp.8, 2017, https://doi.org/10.1007/s00296-017-3693-6
  3. Factors associated with cytomegalovirus infection in children undergoing allogeneic hematopoietic stem-cell transplantation vol.98, pp.4, 2015, https://doi.org/10.1097/md.0000000000014172
  4. Standardization of Antigenemia and qPCR Cut-off Values in Whole Blood for the Detection of Cytomegalovirus Disease in HIV Patients vol.52, pp.None, 2019, https://doi.org/10.1590/0037-8682-0457-2018
  5. Lower gamma globulin level before conditioning is a risk factor for cytomegalovirus antigenemia after pediatric allogeneic stem cell transplantation vol.66, pp.4, 2015, https://doi.org/10.1002/pbc.27586
  6. Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature vol.25, pp.15, 2015, https://doi.org/10.3748/wjg.v25.i15.1899
  7. Comparison of the CMV antigenemia and CMV-DNA QPCR results in haematopoetic stem cells transplanted recipients - A retrospective observational study vol.14, pp.4, 2020, https://doi.org/10.4103/ijot.ijot_38_19
  8. Relationship of Circulating Cytomegalovirus Levels Obtained Through Antigenemia Testing and Quantitative PCR Differs Between Children and Adults vol.40, pp.1, 2020, https://doi.org/10.3343/alm.2020.40.1.88
  9. Prevalent latent human cytomegalovirus genotype b2 in biopsy samples of gastric cancer vol.15, pp.2, 2015, https://doi.org/10.2217/fvl-2019-0117
  10. Plasma cytomegalovirus DNA load predicts outcomes in liver transplant recipients vol.9, pp.1, 2021, https://doi.org/10.1002/iid3.371