Clinical Correlation of Cytomegalovirus Infection with CMV-Specific CD8+ T Cell Immune Competence Score and Lymphocyte Subsets in Solid Organ Transplant Recipients

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Abstract

Introduction

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 PCR 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 (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 (HR 2.84, 95% CI 1.03-11.81; p=.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 vs. 18.8 days, p<.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs. 27.9%; HR 2.56, 95 % CI 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<.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<.0001).

Conclusion

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.

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