Laboratory diagnostic testing for cytomegalovirus infection in solid organ transplant patients

Abstract

Human cytomegalovirus (CMV) infection, which is one of the most common complications in transplant recipients, increases the risk of graft loss and rejection. Laboratory strategies for diagnosing CMV infection rely on the measurement of viral DNAemia and CMV-specific cell-mediated immunity (CMV-CMI). The CMV quantitative nucleic acid amplification test (QNAT) enabled the spread of preemptive therapy and prompted recommendations for surveillance, diagnosis, and monitoring. Despite the implementation of the World Health Organization international standard for calibration, variability of QNAT persists due to technical issues. CMV immunoglobulin G serology is the standard method for CMV immune screening of transplant candidates and donors. Assays for CMV-CMI play an important role in helping to predict the risk and to develop an individualized CMV management plan. Genotypic testing for resistance is needed when drug-resistant CMV infection is suspected. Here, we review the state of the art of laboratory tests for CMV infection in solid organ transplantation.

The influence of HLA A, B, C, DR alleles and HLA haplotypes on cytomegalovirus‐specific cell mediated immunity in seropositive Korean kidney transplant candidates

“…Pretransplant CMV-CMI has been suggested as a risk for posttransplant CMV replication. [2][3][4]17,[21][22][23][24] We selected 44 HLA alleles to analyze the CMV-ELI-SPOT results based on HLA allele frequencies. The frequencies of these 44 HLA alleles in our study were comparable to those found in previous reports (Table S2).…”

“…This requires special attention in identifying risk factors associated with CMV reactivation. Pretransplant CMV‐CMI has been suggested as a risk for posttransplant CMV replication 2–4,17,21–24 …”

“…We simultaneously measured pp65 and IE-1 ELI-SPOT levels in CMV-seropositive transplant candidates using overlapping peptide mixtures to detect both CD4+ and CD8+ T-cell responses. 21,24,31 Although both subsets of T cells are involved in CMV-specific CMI, several studies have suggested that measuring the CMV-specific CD4+ T cell response has better diagnostic utility. 3,22,32 Therefore, experiments with differentiated CMV-specific CD4+ and CD8+ T cells may more accurately reflect the quantification of CMV-CMI.…”

Cytomegalovirus and Kidney Transplantation: An Update

“…CMV-specific IgG antibodies are screened for in both donors and recipients, as serostatus is the most important predictor of CMV risk following transplantation [14,15]. Solid organ transplantation, particularly from seropositive donors (D+) to seronegative patients (R-), confers the single greatest risk for both transmission and developing clinically significant CMV infection [16][17][18][19]. In seronegative recipients, up to 58% of transplant recipients from seropositive donors (D+/R-) can develop clinically significant CMV infections if prophylactic antivirals are not taken, while this risk can be as low as 2.4% if serostatus is D-/R- [5,20].…”

“…Cell and tissue culture, although highly specific, have very limited practical utility in the prevention, diagnosis, and treatment of CMV in SOT patients due to long turnaround time for testing. Despite the growing availability of CMV-specific cell-mediated immune assays such as interferon gamma release assay (QuantiFERON, ELISpot) for posttransplant risk stratification, their role in the prevention and treatment of CMV infection has yet to be established [12,18,62].…”