Immune mechanisms of acute and chronic rejection

Becker, Luis; Morath, Christian; Suesal, Caner

doi:10.1016/j.clinbiochem.2016.02.001

Cited by 39 publications

(33 citation statements)

References 32 publications

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“…Despite substantial improvements in immunosuppressive therapies and surgical techniques, acute rejection (AR) remains a frequent and serious post-transplantation complication, which contributes to late allograft loss and mortality [3, 4]. To date, the gold standard for diagnosing AR relies on multiple and repeated renal allograft biopsies.…”

Section: Introductionmentioning

confidence: 99%

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection

Cao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. Methods: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. Results: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). Conclusion: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.

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Section: Introductionmentioning

confidence: 99%

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection

Cao

et al. 2017

Cell Physiol Biochem

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“…Fifteen per cent of transplant recipients develop acute kidney allograft rejection, which includes T cell‐mediated rejection (TCMR), antibody‐mediated rejection (ABMR) and mixed ABMR/TCMR [2]. TCMR has a relatively good prognosis if treated appropriately [3,4]. In contrast, ABMR has emerged as the major cause of late kidney allograft loss and as a challenging target to reduce transplant failure [3,5].…”

Section: Introductionmentioning

confidence: 99%

Donor‐derived cell‐free DNA as a biomarker for rejection after kidney transplantation: a systematic review and meta‐analysis

et al. 2020

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Summary A systematic review and meta‐analysis were performed to investigate the value of donor‐derived cell‐free DNA (dd‐cfDNA) as a noninvasive biomarker in diagnosing kidney allograft rejection. We searched PubMed, Web of Science and the Cochrane Library for original research papers published between January 1994 and May 2020 on dd‐cfDNA fractions in blood of kidney allograft recipients. A single‐group meta‐analysis was performed by computing pooled estimates for dd‐cfDNA fractions using the weighted median of medians or quantile estimation (QE) approach. Weighted median differences in medians (WMDMs) and median differences based on the QE method were used for pairwise comparisons. Despite heterogeneity among the selected studies, the meta‐analysis revealed significantly higher median dd‐cfDNA fractions in patients with antibody‐mediated rejection (ABMR) than patients without rejection or patients with stable graft function. When comparing patients with T cell‐mediated rejection (TCMR) and patients with ABMR, our two statistical approaches revealed conflicting results. Patients with TCMR did not have different median dd‐cfDNA fractions than patients without rejection or patients with stable graft function. dd‐cfDNA may be a useful marker for ABMR, but probably not for TCMR.

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“…ACR is a T cell cytotoxic immune response against the graft, leading to inflammatory cell infiltration with tubulitis and, eventually, damage of the donor tissue (9,10). The positive outcome of ACR if treated early, as well as its potentially irreversible damage, render it particularly relevant for prevention research (10,11). Regarding non-invasive diagnostics, a number of studies have obtained good results using tissue, blood or urine markers (11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

Wittenbrink

Herrmann

Blázquez-Navarro

et al. 2018

Preprint

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SummaryAcute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA<30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity=76.5%, specificity= 88.9%). The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information.

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Immune mechanisms of acute and chronic rejection

Cited by 39 publications

References 32 publications

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection

A Molecular Signature of Two Long Non-Coding RNAs in Peripheral Blood Predicts Acute Renal Allograft Rejection

Donor‐derived cell‐free DNA as a biomarker for rejection after kidney transplantation: a systematic review and meta‐analysis

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

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