Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968551 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2334 (Electronic) Linking ISSN: 14712334 NLM ISO Abbreviation: BMC Infect Dis Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cytomegalovirus/*immunology ; Immunoassay/*methods; Adult ; Aged ; Area Under Curve ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/metabolism ; Cytokines/metabolism ; Cytomegalovirus/isolation & purification ; Cytomegalovirus Infections/complications ; Cytomegalovirus Infections/diagnosis ; Female ; Flow Cytometry ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/diagnosis ; Hematologic Neoplasms/virology ; Humans ; Linear Models ; Male ; Middle Aged ; Organ Transplantation ; ROC Curve ; Retrospective Studies

Background: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events.
Methods: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event.
Results: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%).
Conclusions: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

Erratum in: BMC Infect Dis. 2020 Feb 11;20(1):122. (PMID: 32046661)

Clin Infect Dis. 2018 Oct 15;67(9):1395-1402. (PMID: 29635432)
Am J Transplant. 2017 Sep;17(9):2468-2473. (PMID: 28500691)
Transpl Infect Dis. 2019 Oct;21(5):e13138. (PMID: 31278878)
Clin Microbiol Infect. 2019 Mar;25(3):381.e1-381.e10. (PMID: 29803844)
Transpl Infect Dis. 2007 Jun;9(2):165-70. (PMID: 17462006)
J Virol. 2012 Jan;86(2):1001-9. (PMID: 22072753)
Clin Vaccine Immunol. 2012 May;19(5):791-6. (PMID: 22379065)
Transplantation. 2001 May 15;71(9):1287-94. (PMID: 11397964)
J Clin Virol. 2018 Aug;105:91-96. (PMID: 29936407)
Clin Transplant. 2019 Sep;33(9):e13512. (PMID: 30817026)
Transplantation. 2018 Jun;102(6):900-931. (PMID: 29596116)
J Clin Virol. 2014 Dec;61(4):523-8. (PMID: 25453571)
J Clin Microbiol. 2013 Aug;51(8):2501-7. (PMID: 23678073)
J Exp Med. 2005 Apr 4;201(7):1031-6. (PMID: 15795239)
Clin Infect Dis. 2013 Mar;56(6):817-24. (PMID: 23196955)
Am J Transplant. 2008 Dec;8(12):2590-9. (PMID: 18853954)
Pathology. 2018 Aug;50(5):554-561. (PMID: 29945729)
J Virol. 2004 Jun;78(11):5535-45. (PMID: 15140950)
PLoS One. 2018 Mar 20;13(3):e0193968. (PMID: 29558479)
Transplantation. 2017 Oct;101(10):e315-e325. (PMID: 28594749)
Nat Rev Immunol. 2012 Jan 20;12(2):136-48. (PMID: 22266691)
Medicine (Baltimore). 2019 Apr;98(16):e15228. (PMID: 31008952)
Transpl Infect Dis. 2016 Apr;18(2):191-201. (PMID: 26878346)
Transpl Infect Dis. 2018 Oct;20(5):e12934. (PMID: 29809312)
Transplantation. 2012 Jan 27;93(2):195-200. (PMID: 22179399)
Ann Hematol. 2017 Jan;96(1):125-131. (PMID: 27730340)
Blood. 2019 Feb 21;133(8):867-877. (PMID: 30573634)
Clin Infect Dis. 2017 Jan 1;64(1):87-91. (PMID: 27682069)
Am J Transplant. 2009 May;9(5):1214-22. (PMID: 19422346)
J Virol. 2017 Feb 28;91(6):. (PMID: 28053099)
PLoS One. 2014 Aug 28;9(8):e106044. (PMID: 25166270)
J Clin Microbiol. 2018 Mar 26;56(4):. (PMID: 29305542)
Open Forum Infect Dis. 2017 Jul 08;4(3):ofx143. (PMID: 28852681)
Circulation. 2006 Oct 10;114(15):1608-15. (PMID: 17015794)
J Clin Microbiol. 2012 Jun;50(6):1974-80. (PMID: 22461674)
Clin Infect Dis. 2017 Nov 29;65(12):2000-2007. (PMID: 29020220)
Am J Respir Crit Care Med. 2016 Jan 1;193(1):78-85. (PMID: 26372850)
Transplantation. 2019 May;103(5):1005-1013. (PMID: 30247316)
BMC Infect Dis. 2018 Apr 16;18(1):179. (PMID: 29661141)
Open Forum Infect Dis. 2018 Sep 11;5(10):ofy230. (PMID: 30302355)
Am J Transplant. 2006 Oct;6(10):2356-64. (PMID: 16889599)
Am J Transplant. 2019 Sep;19(9):2505-2516. (PMID: 30768834)
Transpl Int. 2018 Apr;31(4):436-450. (PMID: 29284181)
Transplant Proc. 2017 Oct;49(8):1766-1772. (PMID: 28923622)
Transplantation. 2018 Nov;102(11):e472-e480. (PMID: 30130330)

Academic Assessment Grant Brown Physicians Inc

Keywords: (val)ganciclovir; CMV; Cytomegalovirus; Immunoassays; Transplantation

0 (Cytokines)

Date Created: 20200119 Date Completed: 20200317 Latest Revision: 20200317

20231215

PMC6969482

10.1186/s12879-020-4787-4

31952516