Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study

BACKGROUND: The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis. METHODS: A pilot study of renal transplant recipient (RTR’s) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR’s were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR’s were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay. RESULTS: At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x10(5) PBMC’s; pp65 ≤ 3 spots / 2.5x10(5) PBMC’s). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x10(5) PBMC’s) and pp65 (>50 spots / 2.5x10(5) PBMC’s), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02). CONCLUSIONS: In CMV seronegative RTR’s, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR’s, associated with protection from CMV infection. In seropositive RTR’s, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group.