TY - JOUR
T1 - Prediction of herpes virus infections after solid organ transplantation
T2 - a prospective study of immune function
AU - Møller, Dina Leth
AU - Sørensen, Søren Schwartz
AU - Rezahosseini, Omid
AU - Rasmussen, Daniel Bräuner
AU - Arentoft, Nicoline Stender
AU - Loft, Josefine Amalie
AU - Perch, Michael
AU - Gustafsson, Finn
AU - Lundgren, Jens
AU - Scheike, Thomas
AU - Knudsen, Jenny Dahl
AU - Ostrowski, Sisse Rye
AU - Rasmussen, Allan
AU - Nielsen, Susanne Dam
N1 - Copyright © 2023 Møller, Sørensen, Rezahosseini, Rasmussen, Arentoft, Loft, Perch, Gustafsson, Lundgren, Scheike, Knudsen, Ostrowski, Rasmussen and Nielsen.
PY - 2023
Y1 - 2023
N2 - INTRODUCTION: Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR.METHODS: All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex.RESULTS: We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001).CONCLUSION: In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.
AB - INTRODUCTION: Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR.METHODS: All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex.RESULTS: We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001).CONCLUSION: In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.
KW - Humans
KW - Infant
KW - Prospective Studies
KW - Interleukin-12 Subunit p40
KW - Epstein-Barr Virus Infections/diagnosis
KW - Herpesvirus 4, Human
KW - Herpesviridae Infections/diagnosis
KW - Organ Transplantation/adverse effects
KW - Cytomegalovirus
KW - Herpesvirus 3, Human
KW - Herpesvirus 2, Human
KW - Cytomegalovirus Infections/epidemiology
KW - Immunity
KW - Poly I
KW - TruCulture®
KW - cytomegalovirus
KW - prediction
KW - solid organ transplantation
KW - immune functional assay
KW - herpes virus
UR - http://www.scopus.com/inward/record.url?scp=85165019315&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1183703
DO - 10.3389/fimmu.2023.1183703
M3 - Journal article
C2 - 37465673
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1183703
ER -