Purpose: Cytomegalovirus (CMV) infection has been implicated in the pathogenesis of allograft rejection, which is reflected by high gene-expression profiling (GEP) scores. In the IMAGE study, patients with D+ or R+ serologies had higher mean GEP scores compared to D-/R- patients, suggesting a latent effect of CMV status on the GEP score. Though active CMV viremia has a distinct molecular signature that is independent from that of acute cellular rejection (ACR), the effect of a CMV infection on serial GEP scores in the absence of ACR is not known.

Method: Data from 239 patients from 11 centers enrolled in Outcomes AlloMap® Registry (OAR) were analyzed. 12 patients (5%) had diagnosis of CMV infection reported. In 11/12 patients, CMV serology at the time of transplant, time to CMV infection, and at least one GEP score, were available. Using linear mixed-effects modeling, the GEP scores at the visit closest to the CMV infection were compared to GEP scores obtained at other visits.

Results: Positive CMV serology at the time of transplant was noted in 11 (100%) patients (D+/R+: n=5; D+/R-: n=6). The mean time to CMV infection from transplant was 282 days. Mean GEP score at the time of diagnosis of CMV infection was significantly higher when compared to GEP score obtained at other visits (33.87 vs. 29.04, p=0.0048). There was no rejection (≥2R or antibody-mediated rejection) present at the time of CMV infection visit.

Conclusion: CMV infections in cardiac transplant recipients are associated with an increase in GEP score that is independent of associated allograft rejection. The likely mechanism is immune activation/modulation of one or more of the 11 genes in the GEP signature. These preliminary data suggest that CMV status should be considered when clinically interpreting high GEP scores in cardiac transplant patients.

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