Dataset Information

Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

ABSTRACT: Background: Rejection continues to be the main cause of renal graft loss. Currently, the gold standard for diagnosis is an allograft biopsy; however, because it is time-consuming, costly, and invasive, the pursuit of novel biomarkers has gained interest. Variation in the expressions of miRNAs is currently considered a probable biomarker for the diagnosis of acute rejection. This study aimed to determine whether miR-150-5p in serum is related to microvascular damage in patients with acute antibody-mediated rejection (ABMR). Methods: A total of 27 patients who underwent renal transplantation (RT) with and without ABMR were included in the study. We performed the quantification of hsa-miR-150-5p, hsa-miR-155, hsa-miR-21, hsa-miR-126, and hsa-miR-1 in plasma by RT-qPCR. The expressions between the groups and their correlations with the histological characteristics of the patients with ABMR were also investigated. Results: miR-150-5p significantly increased in the plasma of patients with rejection (p < 0.05), and the changes in miR-150-5p were directly correlated with microvascular inflammation in the allograft biopsies. Clinical utility was determined by ROC analysis with an area under the curve of 0.873. Conclusions: Our results show that the patients with RT with ABMR exhibited increased expression of miR-150-5p compared to patients without rejection, which could have clinical consequences, as well as probable utility in the diagnosis of ABMR, and bioinformatics may help in unraveling the molecular mechanisms underlying ABMR conditions.

SUBMITTER: Zepeda-Quiroz I

PROVIDER: S-EPMC10971536 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

Zepeda-Quiroz Iván I Guzmán-Martín Carlos A CA Peña-Peña Mario M Juárez-Villa José D JD Soto-Abraham Maria V MV Vázquez-Toledo Miguel A MA Jiménez-Ortega Rogelio F RF Moguel-González Bernardo B Osorio-Alonso Horacio H Sánchez-Muñoz Fausto F Flores-Gama César C

Journal of clinical medicine 20240311 6

<b>Background</b>: Rejection continues to be the main cause of renal graft loss. Currently, the gold standard for diagnosis is an allograft biopsy; however, because it is time-consuming, costly, and invasive, the pursuit of novel biomarkers has gained interest. Variation in the expressions of miRNAs is currently considered a probable biomarker for the diagnosis of acute rejection. This study aimed to determine whether miR-150-5p in serum is related to microvascular damage in patients with acute ...[more]

PMID: 38541826

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Project description:Background and Aims: News strategies for the accurate assessment of the state of immunosuppression (IS) in liver transplant recipients are needed to prevent rejection and minimize drug-related side effects. miRNAs can potentially be used as diagnostic or prognostic biomarkers in transplant patients. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients. Methods: A total of 145 liver recipients were included. All patients received a calcineurin inhibitor with or without mycophenolate mofetil and methylprednisolone. Plasmatic miRNA expression was assessed by qPCR before and at different time-points after liver transplantation. Results: Seventeen patients experienced TCMAR, and eight were diagnosed with SCR during the protocol biopsy at the 3rd month post-transplantation. Pre-transplantation, miR-155-5p expression was significantly higher in TCMAR patients and in SCR patients than in non-rejectors, and miR-181a-5p expression was also significantly higher in SCR patients than in non-rejectors. Post-transplantation, before transaminase-level modification, significantly increased miR-181a-5p, miR-155-5p, and miR-122-5p expression was observed in TCMAR and SCR patients. Binary logistic regression analyses showed, post-transplantation, that TCMAR risk was better predicted by individual expression of miR-181a-5p (LOGIT = -6.35 + 3.87*miR-181a-5p), and SCR risk was better predicted by the combination of miR-181a-5p and miR-155-5p expression (LOGIT = -5.18 + 2.27*miR-181a-5p+1.74*miR-155-5p). Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers.

Project description:BackgroundAntibody-mediated rejection (ABMR) is the main cause of renal allograft loss. The most common treatment strategy is based on plasmapheresis plus the subsequent administration of intravenous immunoglobulin (IVIG). Unfortunately, no approved long-term therapy is available for ABMR. The current study was designed to analyze the effect of various ABMR treatment approaches on allograft survival and to compare treatment effects in the presence or absence of donor-specific antibodies (DSAs).MethodsThis single-center study retrospectively analyzed 102 renal allograft recipients who had biopsy-proven ABMR after transplant. DSA was detectable in 61 of the 102 patients. Initial standard treatment of ABMR consisted of plasmapheresis (PS) or immunoadsorption (IA), followed by a single course of IVIG. In case of nonresponse or recurrence, additional immunosuppressive medications, such as rituximab, bortezomib, thymoglobulin, or eculizumab, were administered. In a second step, persistent ABMR was treated with increased maintenance immunosuppression, long-term therapy with IVIG (more than 1 year), or both.ResultsOverall graft survival among transplant patients with ABMR was <50% after 3 years of follow-up. Compared to the use of PS/IA and IVIG alone, the use of additional immunosuppressive medications had no beneficial effect on allograft survival (p = 0.83). Remarkably, allografts survival rates were comparable between patients treated with the combination of PS/IA and IVIG and those treated with a single administration of IVIG (p = 0.18). Renal transplant patients with ABMR but without DSAs benefited more from increased maintenance immunosuppression than did DSA-positive patients with ABMR (p = 0.01). Recipients with DSA-positive ABMR exhibited significantly better allograft survival after long-term application of IVIG for more than 1 year than did recipients with DSA-negative ABMR (p = 0.02).ConclusionsThe results of our single-center cohort study involving kidney transplant recipients with ABMR suggest that long-term application of IVIG is more favorable for DSA-positive recipients, whereas intensification of maintenance immunosuppression is more effective for recipients with DSA-negative ABMR.

Project description:Acute rejection threatens kidney allograft longevity. Cell-free DNA (cfDNA) is a real-time marker of organ injury and immune response. DNA methylation is an epigenetic marker that regulates gene expression. We aim to elucidate differential methylation of total plasma cfDNA between pediatric kidney transplant recipients in the presence compared to the absence of acute rejection. In doing so, we hope to exploit the property of cfDNA as a real-time biomarker and build on available testing to identify genes and processes participating in acute allograft rejection pathophysiology in kidney transplantation. Twenty plasma cfDNA samples from pediatric kidney transplant recipients were collected at the time of allograft biopsy. Using whole genome bisulfite sequencing (WGBS), differentially methylated cytosines were identified in presence vs absence of acute rejection. Separate analyses were performed comparing those with borderline rejection to those with rejection, and to those without rejection. Differentially methylated cytosines were then assessed for gene associations and pathway enrichments. Acute rejection was present in 7 biopsies, borderline rejection in 4 biopsies, and no rejection in 9 biopsies. In the comparison of acute rejection to non-rejection biopsies, there were 34,356 differentially methylated cytosines corresponding to 1,269 associated genes, and 533 enriched pathways. These numbers were all substantially greater (4x-13x) than the comparisons made between acute rejection against those with borderline rejection, and between non-rejection against borderline rejection. Prominently enriched pathways between samples of individuals with and without acute rejection were related to immune cell regulation, inflammatory response, lipid metabolism, and tryptophan-kynurenine metabolism. Our data suggest methylation plays a role in development of or response to acute kidney allograft rejection. Specifically, differentially methylated pathways associated with acute rejection include those related to immune and inflammatory responses.

Dataset Information

Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

Publications

Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

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