TABLE 2.
Other immunological approaches proposed within the risk assessment for post-transplant CMV infection.
| Immunological biomarker | Rationale | Diagnostic performance, advantages and limitations | Selected studies |
|---|---|---|---|
| Serum immunoglobulin levels | Severe IgG HGG (usually defined by the threshold of <400–500 mg/dL) as a quantitative surrogate of the humoral immune response | Easily available and economical (nephelometry). Potentially reversible by IVIg/SCIg replacement therapy. Lack of specificity for CMV infection risk | [92, 93] |
| Total lymphocyte count | Lymphopenia (usually defined by the threshold of <0.5–0.75 × 103 cells/μL) as a quantitative surrogate of the T-cell-mediated immune response | Easily available and economical. Lack of specificity for CMV infection risk | [94–97] |
| Peripheral blood lymphocyte subpopulations | Enumeration of peripheral blood CD4+ and CD8+ T-cell counts at different post-transplant time points by automated flow cytometry | Less time- and labor-consuming than CMV-CMI monitoring. Lack of specificity for CMV infection risk. Simultaneous risk assessment for other opportunistic infections. Of particular usefulness in patients receiving T-cell-depleting agents | [98, 99] |
| SNP in genes orchestrating innate and adaptive responses (pattern recognition receptors and interferons) | Protective effect associated to SNPs within TLR9 and IFNL3 genes. Risk-conferring effect associated to SNPs within TLR2, MBL2, DC-SIGN, IL10 and IFNG genes | Attempts of polygenic risk scores (lacking external validation). Modest risk modification effect attributable to a given SNP. Lack of dedicated GWAS studies | [100–104] |
| Intracellular ATP production in CD4+ T-cells | Quantification of intracellular ATP release in CD4+ T-cells stimulated with a potent non-specific mitogen (phytohemagglutinin A), which would provide an overall functional evaluation of T-cell-mediated immunity | FDA-approved commercial assay (ImmuKnow®, Cylex). Lack of validated cut-off values to predict CMV infection. Time- and labor-consuming. Potentially affected by sample storage time | [56, 105] |
ATP, adenosine triphosphate; CMV, cytomegalovirus; CMVCMI, cytomegalovirus-specific cell-mediated immunity; FDA, food and drug administration; GWAS, genomed-wide association study; HGG, hypogammaglobulinemia; IVIg, intravenous immunoglobulin; SCIg, subcutaneous immunoglobulin; SNP, single-nucleotide polymorphism.