title: Predictive value of human cytomegalovirus (HCMV) T-cell response in the control of HCMV infection by seropositive solid-organ transplant recipients according to different assays and stimuli.
abstract: Human cytomegalovirus (HCMV) is still the most common viral infection in solid-organ transplant recipients (SOTR). Our study aimed to identify the predictive values of the T-cell response able to protect from HCMV disease, according to different assays. Viral DNA was determined by real-time PCR. The T-cell immune response to HCMV infection was investigated in SOTR according to the following assays and stimuli: cytokine flow cytometry (CFC) after peripheral blood mononuclear cell (PBMC) stimulation with autologous HCMV-infected dendritic cells (iDC) vs three ELISPOT assays using PBMCs stimulated with: 1. HCMV-infected cell lysate (iCL); 2. a pool of 34 epitopic peptides (PP) from different HCMV proteins; 3. a commercial pp65 peptide pool (CPM). ELISPOT results were normalized to T-cell counts. Overall, 51 SOTR were enrolled: 29 (57%) had low viral load (LVL) self-resolving infections, 19 (37%) high viral load (HVL) infections treated with antiviral drugs, and 3 (6%) tissue-invasive disease (TID). At DNAemia peak, ROC analysis showed that CFC-iDC CD4+ and the ELISPOT-iCL assays yielded overlapping area under the curve (AUC) results. The time needed to reconstitute protective T-cell immunity in SOTR with HVL infections was significantly longer with each assay compared to LVL infections. Using the CFC-iDC assay as a reference test (requiring 7 days to complete), the 24h ELISPOT-iCL assay provides similar results in terms of protection prediction from HCMV infection.
authors.affiliation: Laboratori Sperimentali di Ricerca, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gabanti
authors.affiliation: Laboratori Sperimentali di Ricerca, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bruno
authors.affiliation: Department of Nephrology, University of Pavia, and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Scaramuzzi
authors.affiliation: Department of Nephrology, University of Pavia, and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Mangione
authors.affiliation: Laboratori Sperimentali di Ricerca, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zelini
authors.affiliation: Laboratori Sperimentali di Ricerca, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gerna
authors.affiliation: Laboratori Sperimentali di Ricerca, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000517:prevention & control*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000502:physiology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral
keywords: Cytokine flow cytometry; Dendritic cells; ELISPOT; Human cytomegalovirus; Solid-organ transplant recipients; T-cell response