Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY): a retrospective and prospective observational cohort study
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Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY) : a retrospective and prospective observational cohort study. / 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.
I: BMC Infectious Diseases, Bind 23, 2023, s. 214.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Herpesvirus immunology in solid organ transplant recipients - liver transplant study (HISTORY)
T2 - a retrospective and prospective observational cohort study
AU - Suarez-Zdunek, Moises Alberto
AU - Saini, Sunil Kumar
AU - Pedersen, Christian Ross
AU - Hamm, Sebastian Rask
AU - Hald, Annemette
AU - Rasmussen, Allan
AU - Hillingsø, Jens Georg
AU - Hadrup, Sine Reker
AU - Nielsen, Susanne Dam
N1 - Publisher Copyright: © 2023. The Author(s).
PY - 2023
Y1 - 2023
N2 - BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05532540), registered 8 September 2022.
AB - BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05532540), registered 8 September 2022.
KW - Cytomegalovirus infections
KW - Immunodominant Epitopes
KW - Inflammation
KW - Liver transplantation
KW - Major Histocompatibility Complex
KW - T-Lymphocytes
KW - Varicella Zoster Virus infection
U2 - 10.1186/s12879-023-08153-8
DO - 10.1186/s12879-023-08153-8
M3 - Journal article
C2 - 37024811
AN - SCOPUS:85151832592
VL - 23
SP - 214
JO - B M C Infectious Diseases
JF - B M C Infectious Diseases
SN - 1471-2334
ER -
ID: 344642994