Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY): a retrospective and prospective observational cohort study

• Published in: BMC infectious diseases Vol. 23; no. 1; pp. 214 - 6
• Main Authors: Suarez-Zdunek, Moises Alberto, Saini, Sunil Kumar, Pedersen, Christian Ross, Hamm, Sebastian Rask, Hald, Annemette, Rasmussen, Allan, Hillingsø, Jens Georg, Hadrup, Sine Reker, Nielsen, Susanne Dam
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.04.2023; BioMed Central; BMC
• Subjects: Analysis; Antigens; Blood; Cell therapy; Cohort analysis; Cytokines; Cytomegalovirus; Cytomegalovirus infections; Cytomegalovirus Infections - epidemiology; Cytomegalovirus Infections - etiology; Demographic aspects; Denmark; Epidemiology; Evaluation; Flow cytometry; Graft rejection; Health aspects; Herpes; Herpes viruses; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus diseases; Hospitals; Humans; Immune response; Immune response (cell-mediated); Immune system; Immunodominant Epitopes; Immunology; Infection; Infections; Infectious diseases; Inflammation; Laboratories; Leukocytes, Mononuclear; Liver; Liver transplantation; Liver Transplantation - adverse effects; Liver transplants; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical records; Medical research; Medicine, Experimental; Morbidity; Mortality; Observational studies; Organ transplant recipients; Patients; Peptides; Peripheral blood mononuclear cells; Prediction models; Prospective Studies; Questionnaires; Retrospective Studies; Risk factors; Serology; Simplexvirus; T cell receptors; T cells; T-Lymphocytes; Transplant Recipients; Transplantation; Varicella; Varicella Zoster Virus infection; Virus diseases; Denmark; Major Histocompatibility Complex; T-Lymphocytes; Cytomegalovirus infections; Inflammation; Varicella Zoster Virus infection; Immunodominant Epitopes; Liver transplantation
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-023-08153-8

Life-long immunosuppressive treatment after liver transplantation (LT) prevents graft rejection but predisposes the LT recipient to infections. Herpesvirus infections are associated with morbidity and mortality among LT recipients. Among those, especially cytomegalovirus (CMV) and varicella-zoster virus (VZV) pose challenges after LT. The aim of this study is to provide an in-depth characterization of the cellular immune response against CMV and VZV infections in LT recipients and identify potential risk factors for infection. The Herpesvirus Infections in Solid Organ Transplant Recipients - Liver Transplant Study (HISTORY) consists of an epidemiological and immunological substudy. The epidemiological substudy is a retrospective observational cohort study that includes all patients who underwent LT in Denmark between 2010 and 2023 (N ≈ 500). Using data from nationwide hospital records and national health registries, the incidence of and clinical risk factors for CMV and VZV infections will be determined. The immunological substudy is an explorative prospective observational cohort study including patients enlisted for LT in Denmark during a 1.5-year period (N > 80). Participants will be followed with scheduled blood samples until 12 months after LT. CMV- and VZV-derived peptides will be predicted for their likelihood to be presented in participants based on their HLA type. Peptide-MHC complexes (pMHC) will be produced to isolate CMV- and VZV-specific T cells from peripheral blood mononuclear cells before and after CMV and VZV infection. Their frequency, T cell receptor sequences, and phenotypic characteristics will be examined, and in a subset of participants, CMV- and VZV-specific T cells will be expanded ex vivo. This study will provide novel insight into T cell immunity required for viral control of CMV and VZV and has the potential to develop a prediction model to identify LT recipients at high risk for infection based on a combination of clinical and immunological data. Furthermore, this study has the potential to provide proof-of-concept for adoptive T cell therapy against CMV and VZV. Combined, this study has the potential to reduce the burden and consequence of CMV and VZV infections and improve health and survival in LT recipients. ClinicalTrials.gov (NCT05532540), registered 8 September 2022.