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Clinical Correlation of Cytomegalovirus Infection With CMV-specific CD8+ T-cell Immune Competence Score and Lymphocyte Subsets in Solid Organ Transplant Recipients

Meesing, Atibordee MD1,2; Abraham, Roshini S. PhD3; Razonable, Raymund R. MD1,4

doi: 10.1097/TP.0000000000002396
Original Clinical Science—General

Background. Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients.

Methods. During a 10-year period, selected kidney, heart, lung, pancreas, liver, and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production, and CD107a/b degranulation. Quantitative and functional data were used to assemble T-cell immune competence (TIC) score. CMV infection was diagnosed by polymerase chain reaction in blood and other samples or histopathology.

Results. Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (interquartile range [IQR], 5.5–18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (hazard risk, 2.84, 95% confidence interval, 1.03–11.81; P = 0.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 days vs 18.8 d; P < 0.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs 27.9%; hazard risk, 2.56; 95% confidence interval, 1.09–5.89; P = 0.03). Patients with CMV infection or disease had lower median absolute lymphocyte count (380 [IQR, 240–540] vs 940 [IQR, 551–1210] cells/mm3; P < 0.0001) and CD4+ T cell count (29 cells/mm3 [IQR, 1.3–116.0] vs 325.5 cells/mm3 [IQR, 151.5–589.8]; P < 0.0001).

Conclusions. Nonspecific and CMV-specific CD8+ T-cell function correlated with the course of CMV after SOT, and measuring these has the potential to assist in its clinical management.

1 Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN.

2 Division of Infectious Disease and Tropical Medicine, Department of Medicine, Khon Kaen University, Khonkean, Thailand.

3 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

4 William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.

Received 3 April 2018. Revision received 23 July 2018.

Accepted 29 July 2018.

The authors declare no funding or conflicts of interest.

A.M. participated in the performance of the research, data collection and data analysis, and writing of the article. R.A. participated in the data collection and laboratory analysis, and reviewing the article. R.R. participation in research design, data collection and analysis, and writing and approving the article.

Correspondence: Roshini S. Abraham, PhD, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. (

Raymund R. Razonable, MD, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905. (

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