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Simultaneous Monitoring of Cytomegalovirus-Specific Antibody and T-cell levels in Seropositive Heart Transplant Recipients

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Abstract

Purpose

Human cytomegalovirus (CMV) active infection (CMV infection) poses serious risks to CMV-seropositive heart transplant recipients. We evaluated the usefulness of simultaneous assessment of CMV-specific values for parameters of the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in the identification of heart recipients at risk of developing CMV infection after transplantation.

Methods

We prospectively studied 38 CMV-seropositive heart recipients. Anti-CMV antibody titers were assessed using enzyme-linked immunosorbent assays. CD4+ and CD8+ T-cell responses to overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1 (IE1) were evaluated by flow cytometry. Immunological studies were performed before transplantation and at 30 days after transplantation. Patients with CMV infection were compared with heart recipients without CMV infection.

Results

During the 6-month follow-up period, 13 (34.2%) patients developed CMV infection. At baseline, the mean anti-CMV-IgG antibody titer was lower in patients who developed CMV infection. This difference remained at 30 days after transplantation. One month after transplantation, the mean percentage of IE1-specific CD8+ T cells that are IFNg-positive (CD8/IFNg + IE1) was lower in CMV-infected patients. The predictive value of these variables at 30 days was increased when they were combined. Cox regression analysis revealed an association between the risk of developing CMV infection and the combination marker (low anti-CMV titer [<16,100] and low CD8/IFNg + IE1 percentages [<0.40%], relative hazard, 6.07; p = 0.019). The combination marker remained significant after adjustment for clinical variables.

Conclusions

This novel approach of a simultaneous assessment of specific anti-CMV antibody titers and CD8/IFNg + IE1 percentages might help identify heart transplant recipients with an increased risk of developing CMV infection.

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Acknowledgments

We thank members of the Department of Immunology, cardiologists and nursing staff of the Cardiology and Cardiovascular Surgery for their continued support and to the patients for their generous collaboration. N del Pozo performed ELISA tests for specific anti-varicella antibodies. L Valor performed the substudy of lymphoproliferative responses to PHA. M Jaramillo performed ELISA tests for serum IFNg concentration J Romero contributed to the graphic design and Thomas O’Boyle proofread the manuscript.

Funding Sources

This study was supported by grants from the Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria (projects numbers 05/0839, 08/1430), and Grifols International, Barcelona, Spain awarded to Javier Carbone. Elizabeth Sarmiento had a grant from the ERA-EDTA Fellowship Programme administrated by the European Molecular Biology Organization.

Conflict of interest statement

None of the authors have a financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.

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Authors and Affiliations

  1. Transplant Immunology Group, Clinical Immunology Department, Gregorio Marañón Hospital, Dr Esquerdo 46, 28007, Madrid, Spain

    Javier Carbone, Nallibe Lanio, Antonio Gallego, Joaquin Navarro, Eduardo Fernández-Cruz & Elizabeth Sarmiento

  2. Division of Medicine, Brighton and Sussex Medical School, Brighton, UK

    Florian Kern

  3. Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany

    Florian Kern & Elizabeth Sarmiento

  4. Microbiology Department, Gregorio Marañón Hospital, Madrid, Spain

    Patricia Muñoz, Roberto Alonso & Pilar Catalán

  5. Cardiology Department, Gregorio Marañón Hospital, Madrid, Spain

    Juan Fernández-Yáñez & Jesús Palomo

  6. Cardiovascular Surgery Department, Gregorio Marañón Hospital, Madrid, Spain

    Manuel Ruiz

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  1. Javier Carbone
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  2. Nallibe Lanio
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  13. Elizabeth Sarmiento
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Corresponding author

Correspondence to Javier Carbone.

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Carbone, J., Lanio, N., Gallego, A. et al. Simultaneous Monitoring of Cytomegalovirus-Specific Antibody and T-cell levels in Seropositive Heart Transplant Recipients. J Clin Immunol 32, 809–819 (2012). https://doi.org/10.1007/s10875-012-9670-7

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  • DOI: https://doi.org/10.1007/s10875-012-9670-7

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