Infect Chemother.  2017 Sep;49(3):161-175. 10.3947/ic.2017.49.3.161.

Immunological Prediction of Cytomegalovirus (CMV) Replication Risk in Solid Organ Transplantation Recipients: Approaches for Regulating the Targeted Anti-CMV Prevention Strategies

Affiliations
  • 1Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. shhan74@yuhs.ac

Abstract

The current cytomegalovirus (CMV) prevention strategies in solid organ transplantation (SOT) recipients have contributed towards overcoming the detrimental effects caused by CMV lytic infection, and improving the long-term success rate of graft survival. Although the quantification of CMV in peripheral blood is the standard method, and an excellent end-point for diagnosing CMV replication and modulating the anti-CMV prevention strategies in SOT recipients, a novel biomarker mimicking the CMV control mechanism is required. CMV-specific immune monitoring can be employed as a basic tool predicting CMV infection or disease after SOT, since uncontrolled CMV replication mostly originates from the impairment of immune responses against CMV under immunosuppressive conditions in SOT recipients. Several studies conducted during the past few decades have indicated the possibility of measuring the CMV-specific cell-mediated immune response in clinical situations. Among several analytical assays, the most advancing standardized tool is the QuantiFERON®-CMV assay. The T-Track® CMV kit that uses the standardized enzyme-linked immunospot assay is also widely employed. In addition to these assays, immunophenotyping and intracellular cytokine analysis using flow cytometry (with fluorescence-labeled monoclonal antibodies or peptide-major histocompatibility complex multimers) needs to be adequately standardized and validated for potential clinical applications.

Keyword

Cell-mediated immunity; Cytomegalovirus; Immune monitoring; Solid organ transplantation

MeSH Terms

Antibodies, Monoclonal
Cytomegalovirus*
Enzyme-Linked Immunospot Assay
Flow Cytometry
Graft Survival
Immunity, Cellular
Immunophenotyping
Major Histocompatibility Complex
Methods
Monitoring, Immunologic
Organ Transplantation*
Transplants*
Antibodies, Monoclonal

Figure

  • Figure 1 Schematic representation of immune monitoring for cytomegalovirus-specific cell-mediated immune response aIt needs the immunodominant synthetic peptides. These generally comprise of long synthetic peptides (13–22 amino acids) for CD4+ T lymphocyte stimulation, and short synthetic peptides (8–10 amino acids) for CD8+ T lymphocyte stimulation [97]. w/, with; w/o, without; PBMC, peripheral blood mononuclear cell; BAL, bronchoalveolar lavage; CMV, cytomegalovirus; DC, dendritic cell; IE, immediate-early; pp, phosphoprotein; gB, glycoprotein B; CMV-CMI, cytomegalovirus-specific cell-mediated immune response; IFN-γ, interferon-gamma; TNF-α, tumor necrosis factor alpha; CCL, chemokine (C-C motif) ligand; CXCL, C-X-C motif chemokine; ICS, intracellular staining; ELISA, enzyme-linked immunosorbent assay; ELISpot, enzyme-linked immunosorbent spot assay; pMHC, peptide-major histocompatibility complex; CyTOF, cytometry by time of flight; HLA, human leukocyte antigen


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