allograft rejection
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2022 ◽  
Vol 8 (2) ◽  
pp. e1274
Author(s):  
Jason T. Bau ◽  
Lucas Churchill ◽  
Manv Pandher ◽  
Hallgrímur Benediktsson ◽  
Lee Anne Tibbles ◽  
...  

Author(s):  
Dhruva Sharma ◽  
Ganapathy Subramaniam ◽  
Neha Sharma ◽  
Preksha Sharma ◽  
Pooja Sharma

Abstract Purpose Patients with end-stage heart failure who remain symptomatic even with exemplary medical and device therapy are treated with heart transplantation. Multitudes of endeavor have been contrived during the last decennium in the field of noninvasive tests to rule out heart transplant rejection (HTR). In spite of having supportive literature, noninvasive imaging techniques lack acceptable documentation of clinical robustness, and endomyocardial biopsy (EMB) still remains the gold standard. The aim of this review is to shed light on the existing noninvasive radiological modalities to detect rejection among heart transplant recipients. Methods A comprehensive search was conducted for this review article on the basis of literature available including scientific databases of PubMed, Embase, and Google Scholar, using keywords of “Heart transplantation,” “Acute allograft rejection,” “Arrhythmias,” “Echocardiography,” “Speckle tracking echocardiography,” and “Cardiac magnetic resonance imaging” from inception until September 2020. Results After preliminary screening of the databases, details regarding existent noninvasive radiological modalities to detect HTR were gathered and compiled in this review article. Currently, deformation imaging using speckle tracking and T2 time using cardiac magnetic resonance imaging can serve as screening tools based on which further invasive investigations can be planned. Standardization of blood-based and imaging modalities as screening and possible diagnostic tools for rejection would have obvious clinical and financial benefits in the care of growing number of post heart transplant recipients in our country. Conclusion Diagnosis of allograft rejection in heart transplant recipients through noninvasive techniques is demanding. To unravel the potential of noninvasive radiological modalities that can serve as a standard-of-care test, a prospective multicentric study randomizing noninvasive modality as first strategy versus current EMB-based gold standard of care is the need of the hour.


2022 ◽  
Vol 8 ◽  
Author(s):  
Wenyu Xiang ◽  
Shuai Han ◽  
Cuili Wang ◽  
Hongjun Chen ◽  
Lingling Shen ◽  
...  

Acute rejection (AR) is closely associated with renal allograft dysfunction. Here, we utilised RNA sequencing (RNA-Seq) and bioinformatic methods to characterise the peripheral blood mononuclear cells (PBMCs) of patients with acute renal allograft rejection. Pretransplant blood samples were collected from 32 kidney allograft donors and 42 corresponding recipients with biopsies classified as T cell-mediated rejection (TCMR, n = 18), antibody-mediated rejection (ABMR, n = 5), and normal/non-specific changes (non-AR, n = 19). The patients with TCMR and ABMR were assigned to the AR group, and the patients with normal/non-specific changes (n = 19) were assigned to the non-AR group. We analysed RNA-Seq data for identifying differentially expressed genes (DEGs), and then gene ontology (GO) analysis, Reactome, and ingenuity pathway analysis (IPA), protein—protein interaction (PPI) network, and cell-type enrichment analysis were utilised for bioinformatics analysis. We identified DEGs in the PBMCs of the non-AR group when compared with the AR, ABMR, and TCMR groups. Pathway and GO analysis showed significant inflammatory responses, complement activation, interleukin-10 (IL-10) signalling pathways, classical antibody-mediated complement activation pathways, etc., which were significantly enriched in the DEGs. PPI analysis showed that IL-10, VEGFA, CXCL8, MMP9, and several histone-related genes were the hub genes with the highest degree scores. Moreover, IPA analysis showed that several proinflammatory pathways were upregulated, whereas antiinflammatory pathways were downregulated. The combination of NFSF14+TANK+ANKRD 33 B +HSPA1B was able to discriminate between AR and non-AR with an AUC of 92.3% (95% CI 82.8–100). Characterisation of PBMCs by RNA-Seq and bioinformatics analysis demonstrated gene signatures and biological pathways associated with AR. Our study may provide the foundation for the discovery of biomarkers and an in-depth understanding of acute renal allograft rejection.


2022 ◽  
Vol 8 ◽  
Author(s):  
Miriam C. Banas ◽  
Georg A. Böhmig ◽  
Ondrej Viklicky ◽  
Lionel P. Rostaing ◽  
Thomas Jouve ◽  
...  

Background: In an earlier monocentric study, we have developed a novel non-invasive test system for the prediction of renal allograft rejection, based on the detection of a specific urine metabolite constellation. To further validate our results in a large real-world patient cohort, we designed a multicentric observational prospective study (PARASOL) including six independent European transplant centers. This article describes the study protocol and characteristics of recruited better patients as subjects.Methods: Within the PARASOL study, urine samples were taken from renal transplant recipients when kidney biopsies were performed. According to the Banff classification, urine samples were assigned to a case group (renal allograft rejection), a control group (normal renal histology), or an additional group (kidney damage other than rejection).Results: Between June 2017 and March 2020, 972 transplant recipients were included in the trial (1,230 urine samples and matched biopsies, respectively). Overall, 237 samples (19.3%) were assigned to the case group, 541 (44.0%) to the control group, and 452 (36.7%) samples to the additional group. About 65.9% were obtained from male patients, the mean age of transplant recipients participating in the study was 53.7 ± 13.8 years. The most frequently used immunosuppressive drugs were tacrolimus (92.8%), mycophenolate mofetil (88.0%), and steroids (79.3%). Antihypertensives and antidiabetics were used in 88.0 and 27.4% of the patients, respectively. Approximately 20.9% of patients showed the presence of circulating donor-specific anti-HLA IgG antibodies at time of biopsy. Most of the samples (51.1%) were collected within the first 6 months after transplantation, 48.0% were protocol biopsies, followed by event-driven (43.6%), and follow-up biopsies (8.5%). Over time the proportion of biopsies classified into the categories Banff 4 (T-cell-mediated rejection [TCMR]) and Banff 1 (normal tissue) decreased whereas Banff 2 (antibody-mediated rejection [ABMR]) and Banff 5I (mild interstitial fibrosis and tubular atrophy) increased to 84.2 and 74.5%, respectively, after 4 years post transplantation. Patients with rejection showed worse kidney function than patients without rejection.Conclusion: The clinical characteristics of subjects recruited indicate a patient cohort typical for routine renal transplantation all over Europe. A typical shift from T-cellular early rejections episodes to later antibody mediated allograft damage over time after renal transplantation further strengthens the usefulness of our cohort for the evaluation of novel biomarkers for allograft damage.


2021 ◽  
Author(s):  
Jianfeng Yu ◽  
Xiaoqing Chen ◽  
Yingqi Li ◽  
Fen Tang ◽  
Wenru Su ◽  
...  

Abstract Obesity is closely related to exacerbated graft rejection and worse graft survival. High leptin levels, caused by excessive adipose cells in obese individuals, may exert a pivotal role in the pathogenesis of allograft rejection. However, the role and underlying mechanism of leptin in allograft rejection remains unclear. This study explored the role and potential mechanism of leptin in allograft rejection in rats. We performed allogeneic corneal transplantation in rats. The recipients were treated with subconjunctival injections of recombinant rat leptin after transplantation. Clinical evaluation, immunohistological assessment, real-time PCR and flow cytometry were administrated. RAW264.7 macrophages were handled with leptin (3 µg/mL) for 4 hours and then were treated with lipopolysaccharide (10ng/mL) for 24 hours. The culture supernatants were acquired for ELISA. NF-κBp65 activation in RAW264.7 macrophages was detected by western blot. Our results showed that the leptin-treated rats had a significantly reduced corneal graft mean survival time. The number of infiltrating F4/80+CD68+ macrophages increased in the leptin-treated corneal grafts. Monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α) and interleukin 6(IL-6) mRNA expression level was higher in the leptin-treated corneal grafts than in the control allografts. Leptin treatment notably increased the frequency and number of T helper 1 (Th1) cells and T helper 17 (Th17) cells in rat ipsilateral cervical lymph nodes. Leptin enhanced NF-κBp65 activation and promoted MCP-1, TNF-α and IL-6 production in RAW264.7 macrophages. Leptin promoted corneal allograft rejection by enhancing the recruitment and activation of macrophages.


2021 ◽  
Author(s):  
Jae‐Hyung Chang ◽  
Hector Alvarado Verduzco ◽  
Katherine Toma ◽  
Sharlinee Sritharan ◽  
Sumit Mohan ◽  
...  

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