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CMV-Specific T Cell Monitoring Offers Superior Risk Stratification of CMV-Seronegative Kidney Transplant Recipients of a CMV-Seropositive Donor

Schachtner, Thomas MD1,2,3; Stein, Maik BSc2; Reinke, Petra MD, PhD1,2

doi: 10.1097/TP.0000000000001825
Original Clinical Science-General

Background: Detectable cytomegalovirus (CMV)-specific T cells in CMV-seronegative kidney transplant recipients (KTRs) have been attributed to an absence of circulating antibodies despite CMV sensitization. The diagnostic value of CMV-specific T cells, however, needs to be implemented in risk stratification for CMV replication.

Methods: Three hundred twenty-six KTRs were studied and classified with respect to CMV serostatus and presence of CMV-specific T cells. Samples were collected pretransplantation, at +1, +2, and +3 months posttransplantation. CMV-specific T cells directed to CMV-IE1 and CMV-pp65 were measured by interferon-γ Elispot assay.

Results: Nineteen (28%) of 67 D+R− KTRs showed pretransplant CMV-specific T cells. Although no differences were observed for CMV replication, KTRs with CMV-specific T cells presented with lower initial and peak CMV loads (P < 0.05). KTRs with decreasing/undetectable CMV-IE1–specific T cells pretransplantation and posttransplantation were at greatest risk of CMV replication. KTRs with stable/increasing CMV-IE1–specific T cells from pretransplantation to posttransplantation, however, showed low risk of CMV replication (P < 0.001). One hundred sixty-two (80%) of 203 R+ KTRs showed pretransplant CMV-specific T cells. Decreasing/undetectable CMV-IE1–specific T cells from pretransplantation and posttransplantation identified those R+ KTRs at increased risk of CMV replication (65/80 KTRs; 81%; P < 0.001).

Conclusions: Despite CMV prophylaxis, D+R− KTRs are at greatest risk of CMV disease. Our data suggest that monitoring CMV-specific T cell kinetics from pretransplantation to posttransplantation, particularly directed to CMV-IE1, offers superior risk stratification compared with CMV serostatus alone.

Nearly 30% of CMV D+/R- serostatus and 80% of R+ serostatus kidney transplant recipients have pretransplant CMV-immediate early antigen 1 (CMV-IE1)-specific T cells and are at low risk of CMV. Those with decreasing or undetectable CMV-IE1-specific T cells pre- and posttransplantation are at greatest risk of CMV-replication.

1 Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.

2 Berlin-Brandenburg Center of Regenerative Therapies (BCRT), Berlin, Germany.

3 Berlin Institute of Health (BIH)-Charité and Max-Delbrück Center, Berlin, Germany.

Received 22 February 2017. Revision received 24 April 2017.

Accepted 10 May 2017.

The authors declare no funding or conflicts of interest.

T.S. participated in data collection, writing of the article, performance of the research, and data analysis. M.S. participated in the performance of the research. P.R. participated in research design, writing of the article, and data analysis.

Correspondence: Thomas Schachtner, MD, Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany. (thomas.schachtner@charite.de).

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