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miRNA rejection

R Roat, M M Hossain, J Christopherson, C Free, S Jain, C Guay, R Regazzi, Z Guo
Currently there is no effective approach for monitoring early β cell loss during islet graft rejection following human islet transplantation (HIT). Due to ethical and technical constraints, it is difficult to directly study biomarkers of islet destruction in humans. Here, we established a humanized mouse model with induced human β cell death using adoptive lymphocyte transfer (ALT). Human islet grafts of ALT-treated mice had peri-graft lymphocyte infiltration, fewer insulin(+) β cells, and increased β cell apoptosis...
October 3, 2016: American Journal of Transplantation
Mareen Matz, Christine Lorkowski, Katharina Fabritius, Pawel Durek, Kaiyin Wu, Birgit Rudolph, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
The potential diagnostic value of circulating free miRNAs in plasma compared to miRNA expression in blood cells for rejection processes after kidney transplantation is largely unknown, but offers the potential for better and timely diagnosis of acute rejection. Free microRNA expression of specific blood cell markers was measured in 160 plasma samples from kidney transplant patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection, interstitial fibrosis and tubular atrophy, antibody-mediated rejection (ABMR), Borderline (Banff3), tubulo-interstitial (Banff4-I) and vascular rejection (Banff4-II/III) applying RT-PCR...
September 20, 2016: Transplant Immunology
Stefano Di Carlo, Elena Rossi, Gianfranco Politano, Simona Inghilleri, Patrizia Morbini, Fiorella Calabrese, Alfredo Benso, Alessandro Savino, Emanuela Cova, Davide Zampieri, Federica Meloni
The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development...
2016: PloS One
Abraham Shaked, Bao-Li Chang, Michael R Barnes, Peter Sayre, Yun R Li, Smita Asare, Michele DesMarais, Michael V Holmes, Toumy Guettouche, Brendan J Keating
: The ability to noninvasively diagnose acute cellular rejection (ACR) with high specificity and sensitivity would significantly advance personalized liver transplant recipient care and management of immunosuppression. We performed microRNA (miRNA) profiling in 318 serum samples from 69 liver transplant recipients enrolled in the Immune Tolerance Network immunosuppression withdrawal (ITN030ST) and Clinical Trials in Organ Transplantation (CTOT-03) studies. We quantified serum miRNA at clinically indicated and/or protocol biopsy events (n = 130)...
August 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Antonietta Picascia, Vincenzo Grimaldi, Claudio Napoli
The complex polymorphism of the HLA genes and the need of a proper identification of anti-HLA antibodies have led to continuously develop novel practical and feasible technologies in the field of organ and tissue transplantation. Technologies to identify HLA molecules have evolved from the serological to the molecular methods and a true innovation in the DNA sequencing has taken place with the development of next generation sequencing. An interesting field to explore is how the information resulting from the HLA-DNA sequencing can be applied in the clinical setting by including the alloimmunization assessment...
October 2016: Transplantation Reviews
Ming Zhou, Hidetaka Hara, Yifan Dai, Lisha Mou, David K C Cooper, Changyou Wu, Zhiming Cai
Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease...
2016: International Journal of Molecular Sciences
Rosa Bianca Schmuck, Anja Reutzel-Selke, Nathanael Raschzok, Mehmet Haluk Morgul, Benjamin Struecker, Steffen Lippert, Cynthia de Carvalho Fischer, Moritz Schmelzle, Sabine Boas-Knoop, Marcus Bahra, Andreas Pascher, Johann Pratschke, Igor M Sauer
CONTEXT: Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT). METHODS: Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients. RESULTS: Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR...
June 27, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Kenta Iwasaki, Takayuki Yamamoto, Yukiko Inanaga, Takahisa Hiramitsu, Yuko Miwa, Kenta Murotani, Shuji Narumi, Yoshihiko Watarai, Akio Katayama, Kazuharu Uchida, Takaaki Kobayashi
De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p < 0.01) underexpressed in patients with DSA. After DSA production, miR-486-5p and its target PTEN/foxO3 mRNA were significantly overexpressed (p < 0...
July 7, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Anchen Zhang, Ke Wang, Cheng Zhou, Zheng Gan, Dongxia Ma, Ping Ye, Yuan Sun, Jie Wu, Xiaofan Huang, Lingyun Ren, Peng Deng, Chuangyan Wu, Zhang Yue, Xiangchao Ding, Jiuling Chen, Jiahong Xia
BACKGROUND: MicroRNAs (miRNAs) are integral for maintaining immune homeostasis and self-tolerance. The influence of miRNAs on T-cell differentiation and plasticity are critical in the development of chronic rejection of transplanted hearts. In this study, we sought to determine whether the knockout of miR-155 affects the development of cardiac allograft vasculopathy (CAV) in a murine model. METHODS: miRNA microarray and quantitative polymerase chain reaction (qPCR) analyses were performed for allograft neointimal lesion samples in chronic rejection...
May 6, 2016: Journal of Heart and Lung Transplantation
M Gunasekaran, Z Xu, D K Nayak, M Sharma, R Hachem, R Walia, R M Bremner, M A Smith, T Mohanakumar
The immunological role of exosomes in allograft rejection remains unknown. We sought to determine whether exosomes are induced during lung allograft rejection and to define the antigenic compositions of HLA, lung-associated self-antigens (SAgs) and microRNAs (miRNAs). Exosomes were isolated from sera and bronchoalveolar lavage fluid from 30 lung transplant recipients (LTxRs) who were stable or who had acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Exosomes were defined by flow cytometry for CD63 and western blotting for annexin V SAgs, collagen V (Col-V) and Kα1 tubulin were examined by electron microscopy; miRNAs were profiled by a miRNA array...
June 9, 2016: American Journal of Transplantation
Shameem S Ladak, Chris Ward, Simi Ali
Lung transplantation (LT) has proven to be successful in carefully selected individuals with end-stage lung disease. However, long-term graft survival post-LT is often hindered by the development of the bronchiolitis obliterans syndrome (BOS). Because BOS represents is a major problem for all LT centers, early identification and prediction of progressive loss of lung function is a major goal. MicroRNAs (miRNAs) play a major role in regulating many cellular functions, including epithelial-to-mesenchymal transition...
May 2016: Journal of Heart and Lung Transplantation
Matthew James Vitalone, Liang Wei, Masato Fujiki, Audrey H Lau, Erik Littau, Carlos Esquivel, Olivia M Martinez, Sheri M Krams
BACKGROUND: Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total lymphoid irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. METHODS: To identify the miRNAs associated with TLI-induced tolerance, we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (Dark Agouti→Lewis) of orthotropic liver transplants that received posttransplant TLI, allogeneic recipients that were not treated posttransplantation and experienced acute rejection, and native Dark Agouti livers...
April 2016: Transplantation
Bhaskar Dutta, Alaleh Azhir, Louis-Henri Merino, Yongjian Guo, Swetha Revanur, Piyush B Madhamshettiwar, Ronald N Germain, Jennifer A Smith, Kaylene J Simpson, Scott E Martin, Eugen Buehler, Eugen Beuhler, Iain D C Fraser
RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis...
2016: Nature Communications
Min-su Kim, Benjamin Hur, Sun Kim
BACKGROUND: RNA-editing is an important post-transcriptional RNA sequence modification performed by two catalytic enzymes, "ADAR"(A-to-I) and "APOBEC"(C-to-U). By utilizing high-throughput sequencing technologies, the biological function of RNA-editing has been actively investigated. Currently, RNA-editing is considered to be a key regulator that controls various cellular functions, such as protein activity, alternative splicing pattern of mRNA, and substitution of miRNA targeting site...
2016: BMC Genomics
Basma Merhi, George Bayliss, Reginald Y Gohh
Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred...
December 24, 2015: World Journal of Transplantation
P Zhang, Z Guo, K Zhong, Q Li, J Ouyang, M Chen, A Hu, X Jiao, X Zhu, X He
OBJECTIVE: This study aimed to document the difference of immunophenotypes in peripheral blood mononuclear cells (PBMCs) between long-term stable liver transplant recipients and recipients with acute rejection. We also sought to identify whether there is any correlation between microRNA (miRNA) expression profile and the differential immunoprofile in these 2 groups to establish a specific miRNA biomarker to identify potential liver transplant recipients. METHODS: PBMCs were isolated from 53 stable liver transplant recipients (STA group) and 15 liver transplant recipients with repeated biopsy-proven rejection episodes admitted to our hospital...
December 2015: Transplantation Proceedings
Kíra Jelencsics, Rainer Oberbauer
The kidney serves as the main clearance organ of our body, filtrating and excreting metabolic waste products. Various intrinsic and extrinsic conditions can lead to kidney injury, roughly 0.1% of the population suffer from end stage renal disease. Renal transplantation reinstitutes an almost normal quality of life; again it is cost effective and thus the preferred treatment of terminal renal failure. miRNAs play pivotal roles in immune responses and inflammation, which makes them particularly interesting in the field of transplantation and in understanding the molecular pathways of allograft pathologies such as delayed function or cellular and antibody mediated rejection...
2015: Advances in Experimental Medicine and Biology
Kebo Zhong, Peng Zhang, Xiaoshun He, Xiaofeng Zhu
OBJECTIVE: To determine whether the miRNA expression profile in peripheral blood mononuclear cells (PBMCs) differs between liver transplant recipients with long-term stable survival and those with acute rejection. METHODS: Twenty-nine liver transplant recipients with long-term stable survival (STA) group, 10 recipients with acute rejection (RJ group), and 17 healthy subjects (control group) were recruited for genome-wide microarray analysis of miRNA expressions in the PBMCs...
November 2015: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Mareen Matz, Katharina Fabritius, Christine Lorkowski, Michael Dürr, Jens Gaedeke, Pawel Durek, Joachim R Grün, Anne Goestemeyer, Friederike Bachmann, Kaiyin Wu, Birgit Rudolph, Danilo Schmidt, Ulrike Weber, Claudia Haftmann, Nadine Unterwalder, Nils Lachmann, Andreas Radbruch, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
BACKGROUND: MicroRNAs (miRNAs, miR) hold important roles in the posttranscriptional regulation of gene expression. Their function has been correlated with kidney disease, and they might represent a new class of biomarkers for frequent evaluation of renal graft status. We analyzed their potential in identifying severe T cell-mediated vascular rejection (TCMVR) (Banff 4-II/III) in kidney transplanted patients. METHODS: Microarray experiments and semiquantitative real-time reverse transcription polymerase chain reaction were performed with total RNA isolated from blood cells of kidney graft recipients...
April 2016: Transplantation
Shao-Chun Wu, Cheng-Shyuan Rau, Johnson Chia-Shen Yang, Tsu-Hsiang Lu, Yi-Chan Wu, Yi-Chun Chen, Siou-Ling Tzeng, Chia-Jung Wu, Chia-Wei Lin, Ching-Hua Hsieh
BACKGROUND: This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation in the presence and absence of FK506 immunosuppression. METHODS: A 1 cm BALB/c donor sciatic nerve graft was transplanted into the sciatic nerve gaps created in recipient C57BL/6 mice with or without daily FK506 immunosuppression [1 mg/(kg·d)]. At 3, 7, and 14 d after nerve allotransplantation, serum samples were collected for miRNA expression analysis by Illumina small RNA deep sequencing...
2015: Disease Markers
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