Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: A multicenter cohort study

Oriol Manuel, Shahid Husain, Deepali Kumar, Carlos Zayas, Steve Mawhorter, Marilyn E. Levi, Jayant Kalpoe, Luiz Lisboa, Leticia Ely, Daniel R. Kaul, Brian S. Schwartz, Michele I. Morris, Michael G. Ison, Belinda Yen-Lieberman, Anthony Sebastian, Maha Assi, Atul Humar

Research output: Contribution to journalArticle

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Abstract

Background. Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D+/R-) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. Methods. We prospectively included D+/R - patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon- levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. Results. Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P <. 001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI],. 74-.98) and 0.27 (95% CI,. 18-.37), respectively. Conclusions. This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis.

Original languageEnglish (US)
Pages (from-to)817-824
Number of pages8
JournalClinical Infectious Diseases
Volume56
Issue number6
DOIs
StatePublished - Mar 15 2013

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Cytomegalovirus
Cellular Immunity
Multicenter Studies
Cohort Studies
Transplants
Transplant Recipients
Confidence Intervals
Antigens
Incidence
Mitogens
Interferons
Antiviral Agents
Tissue Donors

Keywords

  • Quantiferon-CMV
  • antiviral prophylaxis
  • late-onset CMV disease
  • protection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients : A multicenter cohort study. / Manuel, Oriol; Husain, Shahid; Kumar, Deepali; Zayas, Carlos; Mawhorter, Steve; Levi, Marilyn E.; Kalpoe, Jayant; Lisboa, Luiz; Ely, Leticia; Kaul, Daniel R.; Schwartz, Brian S.; Morris, Michele I.; Ison, Michael G.; Yen-Lieberman, Belinda; Sebastian, Anthony; Assi, Maha; Humar, Atul.

In: Clinical Infectious Diseases, Vol. 56, No. 6, 15.03.2013, p. 817-824.

Research output: Contribution to journalArticle

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 2013, 'Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: A multicenter cohort study', Clinical Infectious Diseases, vol. 56, no. 6, pp. 817-824. https://doi.org/10.1093/cid/cis993
Manuel, Oriol ; Husain, Shahid ; Kumar, Deepali ; Zayas, Carlos ; Mawhorter, Steve ; Levi, Marilyn E. ; Kalpoe, Jayant ; Lisboa, Luiz ; Ely, Leticia ; Kaul, Daniel R. ; Schwartz, Brian S. ; Morris, Michele I. ; Ison, Michael G. ; Yen-Lieberman, Belinda ; Sebastian, Anthony ; Assi, Maha ; Humar, Atul. / Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients : A multicenter cohort study. In: Clinical Infectious Diseases. 2013 ; Vol. 56, No. 6. pp. 817-824.
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abstract = "Background. Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D+/R-) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. Methods. We prospectively included D+/R - patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon- levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. Results. Overall, 28 of 127 (22{\%}) patients developed CMV disease. Of 124 evaluable patients, 31 (25{\%}) had a positive result, 81 (65.3{\%}) had a negative result, and 12 (9.7{\%}) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4{\%} vs 22.2{\%} vs 58.3{\%}, respectively; P <. 001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95{\%} confidence interval [CI],. 74-.98) and 0.27 (95{\%} CI,. 18-.37), respectively. Conclusions. This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis.",
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T1 - Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients

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AU - Manuel, Oriol

AU - Husain, Shahid

AU - Kumar, Deepali

AU - Zayas, Carlos

AU - Mawhorter, Steve

AU - Levi, Marilyn E.

AU - Kalpoe, Jayant

AU - Lisboa, Luiz

AU - Ely, Leticia

AU - Kaul, Daniel R.

AU - Schwartz, Brian S.

AU - Morris, Michele I.

AU - Ison, Michael G.

AU - Yen-Lieberman, Belinda

AU - Sebastian, Anthony

AU - Assi, Maha

AU - Humar, Atul

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N2 - Background. Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D+/R-) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. Methods. We prospectively included D+/R - patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon- levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. Results. Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P <. 001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI],. 74-.98) and 0.27 (95% CI,. 18-.37), respectively. Conclusions. This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis.

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