T cell–mediated response to SARS‐CoV‐2 in liver transplant recipients with prior COVID‐19

2021

Abstract Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2‐specific T‐cell‐mediated immunity (SARS‐CoV‐2‐CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS‐CoV‐2‐CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)‐γ FluoroSpot assay after a median of 103 days from COVID‐19 diagnosis. Serum SARS‐CoV‐2 IgG antibodies were measured by ELISA. A control group of non‐transplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post‐transplant SARS‐CoV‐2‐CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN‐γ‐producing CD4+ than …

Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation

2019

SARS-CoV-2-specific Cell-mediated Immunity in Kidney Transplant Recipients Recovered From COVID-19.

2021

BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-I³-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1…

Human genetic polymorphisms and risk of viral infection after solid organ transplantation.

2021

The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomegalovirus (CMV) infection or disease has been att…

Cytomegalovirus infection in solid organ transplantation.

2012

Cytomegalovirus infection remains a serious threat to solid transplant recipients. Despite advances in this field, there are still difficulties in the diagnosis of the disease and there are questions about the best and most cost-effective strategy to prevent infection and its direct and indirect consequences in the short and long term. All these points are discussed and updated in this chapter.

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

2019

The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P  = …

Polymorphisms within the TNFSF4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the cont…

2020

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a twostage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungi…

A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score

2020

Abstract Background We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients. Methods Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI. Results Overall, 309 SOT recipients were followed-up for a median of 1000 da…

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

2015

Background This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. Methods A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69+/interferon-γ-producing CD8+ and CD4+ T cells by flow cytometry for intracellular cytok…

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

2016

Cytomegalovirus (CMV) infection remains a major complication of solid organ transplantation. Because of management of CMV is variable among transplant centers, in 2011 the Spanish Transplantation Infection Study Group (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) developed consensus guidelines for the prevention and treatment of CMV infection in solid organ transplant recipients. Since then, new publications have clarified or questioned the aspects covered in the previous document. For that reason, a panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, tre…

Regular monitoring of cytomegalovirus-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the imme…

2018

Abstract Objective Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. Methods We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptide…