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
Abstract 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 tim...
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| Format: | Article |
| Language: | English |
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BMC
2020-01-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-020-4787-4 |
| _version_ | 1819054621107159040 |
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| author | Ralph Rogers Kapil Saharia Aditya Chandorkar Zoe F. Weiss Kendra Vieira Sophia Koo Dimitrios Farmakiotis |
| author_facet | Ralph Rogers Kapil Saharia Aditya Chandorkar Zoe F. Weiss Kendra Vieira Sophia Koo Dimitrios Farmakiotis |
| author_sort | Ralph Rogers |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T12:54:32Z |
| format | Article |
| id | doaj.art-1aebd4ce087a4dbf9e7366690d0606f0 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-21T12:54:32Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-1aebd4ce087a4dbf9e7366690d0606f02022-12-21T19:03:22ZengBMCBMC Infectious Diseases1471-23342020-01-0120111110.1186/s12879-020-4787-4Clinical 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 eventsRalph Rogers0Kapil Saharia1Aditya Chandorkar2Zoe F. Weiss3Kendra Vieira4Sophia Koo5Dimitrios Farmakiotis6Division of Infectious Diseases, Department of Internal Medicine, Warren Alpert Medical School of Brown UniversityDivision of Infectious Diseases and Institute of Human Virology, University of Maryland School of MedicineDivision of Infectious Diseases and Institute of Human Virology, University of Maryland School of MedicineDivision of Infectious Diseases, Department of Internal Medicine, Warren Alpert Medical School of Brown UniversityDivision of Infectious Diseases, Department of Internal Medicine, Warren Alpert Medical School of Brown UniversityDivision of Infectious Diseases, Department of Internal Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Infectious Diseases, Department of Internal Medicine, Warren Alpert Medical School of Brown UniversityAbstract 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.https://doi.org/10.1186/s12879-020-4787-4CMVCytomegalovirusTransplantationImmunoassays(val)ganciclovir |
| spellingShingle | Ralph Rogers Kapil Saharia Aditya Chandorkar Zoe F. Weiss Kendra Vieira Sophia Koo Dimitrios Farmakiotis 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 BMC Infectious Diseases CMV Cytomegalovirus Transplantation Immunoassays (val)ganciclovir |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | CMV Cytomegalovirus Transplantation Immunoassays (val)ganciclovir |
| url | https://doi.org/10.1186/s12879-020-4787-4 |
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