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Brian J Nankivell, Nidhi Agrawal, Ankit Sharma, Anne Taverniti, Chow H P'Ng, Meena Shingde, Germaine Wong, Jeremy R Chapman
The pathological diagnosis of borderline rejection (BL-R) denotes possible T cell mediated rejection (TCMR), but its clinical significance is uncertain. This single-centre, cross-sectional cohort study compared the functional and histological outcomes of consecutive BL-R diagnoses (n=146) against normal controls (n=826) and acute TCMR (n=55) from 551 renal transplant recipients. BL-R was associated with: contemporaneous renal dysfunction, acute tubular necrosis and chronic tubular atrophy (P<0.001); progressive tubular injury with fibrosis by longitudinal sequential histology (45...
November 30, 2018: American Journal of Transplantation
Philip F Halloran, Arthur Matas, Bertram L Kasiske, Katelynn Madill-Thomsen, Martina Mackova, Konrad S Famulski
In kidney transplant biopsies, inflammation in areas of atrophy-fibrosis (i-IFTA) is associated with increased risk of failure, presumably because inflammation is evoked by recent parenchymal injury from rejection or other insults, but some cases also have rejection. The present study explored the frequency of rejection in i-IFTA, by histology Banff 2015 and microarray-based molecular diagnostic system (MMDx). In unselected indication biopsies (108 i-IFTA, 73 uninflamed IFTA (i0-IFTA), and 53 no IFTA), i-IFTA biopsies were later, more scarred, and had more antibody-mediated rejection (ABMR) by histology (28%) and MMDx (45%)...
November 12, 2018: American Journal of Transplantation
Saleh Yazdani, Jasper Callemeyn, Stéphane Gazut, Evelyne Lerut, Henriette de Loor, Max Wevers, Line Heylen, Carole Saison, Alice Koenig, Olivier Thaunat, Lieven Thorrez, Dirk Kuypers, Ben Sprangers, Laure-Hélène Noël, Leentje Van Lommel, Frans Schuit, Marie Essig, Wilfried Gwinner, Dany Anglicheau, Pierre Marquet, Maarten Naesens
Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways...
November 2, 2018: Kidney International
Mareen Matz, Frederik Heinrich, Qiang Zhang, Christine Lorkowski, Evelyn Seelow, Kaiyin Wu, Nils Lachmann, Richard Kwasi Addo, Pawel Durek, Mir-Farzin Mashreghi, Klemens Budde
CONTEXT: Antibody-mediated rejection (ABMR) after kidney transplantation (KTx) remains the crucial obstacle to successful long-term graft function. The identification of gene signatures involved in ABMR could grant the basis for better prevention and treatment strategies. OBJECTIVE: The identification of gene signatures in whole blood cells specific for ABMR after kidney transplantation. MATERIAL AND METHODS: Total RNA from blood cells of 16 kidney transplanted patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated...
October 20, 2018: Clinical Transplantation
Philip F Halloran, Jeff Reeve, Arezu Z Aliabadi, Martin Cadeiras, Marisa G Crespo-Leiro, Mario Deng, Eugene C Depasquale, Johannes Goekler, Xavier Jouven, Daniel H Kim, Jon Kobashigawa, Alexandre Loupy, Peter Macdonald, Luciano Potena, Andreas Zuckermann, Michael D Parkes
BACKGROUND: Because injury is universal in organ transplantation, heart transplant endomyocardial biopsies present an opportunity to explore response to injury in heart parenchyma. Histology has limited ability to assess injury, potentially confusing it with rejection, whereas molecular changes have potential to distinguish injury from rejection. Building on previous studies of transcripts associated with T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), we explored transcripts reflecting injury...
October 18, 2018: JCI Insight
Cornelius C Thaiss, Tetsu Oura, Hajime Sasaki, Abbas Dehnadi, Masatoshi Matsunami, Ivy A Rosales, Benedict A Cosimi, Tatsuo Kawai
BACKGROUND: Although induction of durable mixed chimerism is required for murine skin allograft tolerance, renal allograft tolerance has been achieved after induction of only transient mixed chimerism in nonhuman primates (NHPs) and humans. To better define the level/duration of chimerism required for stable renal allograft tolerance, we retrospectively analyzed these parameters and compared them with transplant outcomes in NHP combined kidney and bone marrow transplant (CKBMT) recipients...
October 8, 2018: Transplantation
Peng Liu, George Tseng, Zijie Wang, B S Yuchen Huang, Parmjeet Randhawa
Molecular diagnosis is being increasingly used into transplant pathology to render more objective and quantitative determinations that also provide mechanistic and prognostic insights. This study performed RNA-Seq on biopsies from kidneys with stable function (STA) and biopsies with classical findings of T-cell mediated rejection (TCMR). Machine learning tools were used to develop prediction models for distinguishing TCMR and STA samples using the top genes identified by DSeq2. The prediction models were tested on 703 biopsies with Affymetrix chip gene expression profiles available in the public domain...
October 5, 2018: Human Pathology
Steffen Bobka, Nadja Ebert, Eloed Koertvely, Johannes Jacobi, Michael Wiesener, Maike Büttner-Herold, Kerstin Amann, Christoph Daniel
BACKGROUND/AIMS: Complement activation is important in post-transplantation renal injury, but data on its role as predictor of transplant outcome/complications when assessed in donor kidneys are lacking. METHODS: In human renal transplant biopsies with delayed graft function (DGF, n=12), antibody mediated rejection (ABMR, n=8), T-cell mediated rejection (TCMR, n=11), 1 year protocol biopsies (control, n=10) and corresponding zero-biopsies we performed immunohistochemical analyses of 6 complement factors using FFPE sections and correlated the findings with kidney function, as assessed by serum creatinine, and morphological changes including interstitial fibrosis and tubular atrophy (IF/TA)...
2018: Kidney & Blood Pressure Research
Jeong-Hoon Lim, Chan-Hyeong Lee, Kyu Yeun Kim, Hee-Yeon Jung, Ji-Young Choi, Jang-Hee Cho, Sun-Hee Park, Yong-Lim Kim, Moon-Chang Baek, Jae Berm Park, Young-Hoon Kim, Byung Ha Chung, Sang-Ho Lee, Chan-Duck Kim
BACKGROUND: Acute rejection is hazardous to graft survival in kidney transplant recipients (KTRs). We aimed to identify novel biomarkers for early diagnosis of acute T cell-mediated rejection (TCMR) in urinary exosomes of KTRs. METHODS: Among 458 graft biopsies enrolled in a cross-sectional multicenter study, 22 patients with stable graft function (STA) who had not shown pathologic abnormality and 25 patients who diagnosed biopsy-proven TCMR were analyzed. We performed proteomic analysis using nano-ultra performance liquid chromatography-tandem mass spectrometry (nano-UPLC-MS/MS) to identify candidate biomarkers for early TCMR diagnosis on urinary exosomes...
2018: PloS One
Sandy Feng, John C Bucuvalas, Anthony J Demetris, Bryna E Burrell, Katherine M Spain, Sai Kanaparthi, John C Magee, David Ikle, Andrew Lesniak, Juan J Lozano, Estella M Alonso, Robert A Bray, Nancy E Bridges, Edward Doo, Howard M Gebel, Nitika A Gupta, Ryan W Himes, Annette M Jackson, Steven J Lobritto, George V Mazariegos, Vicky L Ng, Elizabeth B Rand, Averell H Sherker, Shikha Sundaram, Yumirle P Turmelle, Alberto Sanchez-Fueyo
BACKGROUND & AIMS: A substantial proportion of pediatric liver transplant recipients develop subclinical chronic allograft injury. We studied whether there are distinct patterns of injury based on histopathologic features and identified associated immunologic profiles. METHODS: We conducted a cross-sectional study of 157 stable, long-term pediatric recipients of transplanted livers (70 boys; > 6 years old at time of transplantation; mean, 8.9 ± 3.46 years after liver transplantation) who underwent liver biopsy analysis from August 13, 2012, through May 1, 2014...
August 23, 2018: Gastroenterology
Aleksandar Senev, Maarten Coemans, Evelyne Lerut, Vicky Van Sandt, Liesbeth Daniëls, Dirk Kuypers, Ben Sprangers, Marie-Paule Emonds, Maarten Naesens
In this cohort study (n = 935 transplantations), we investigated the phenotype and risk of graft failure in patients with histological criteria for antibody-mediated rejection (ABMR) in the absence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA), and compared this to patients with definite ABMR and HLA-DSA-positivity. The histological picture did not differ between HLA-DSA-positive (n = 85) and HLA-DSA-negative (n = 123) cases of ABMR histology, apart from increased complement split product 4d (C4d) deposition in the peritubular capillaries in HLA-DSA-positive cases...
August 14, 2018: American Journal of Transplantation
Mareen Matz, Frederik Heinrich, Christine Lorkowski, Kaiyin Wu, Jens Klotsche, Qiang Zhang, Nils Lachmann, Pawel Durek, Klemens Budde, Mir-Farzin Mashreghi
Interstitial fibrosis/tubular atrophy (IFTA) is associated with reduced allograft survival, whereas antibody-mediated rejection (ABMR) is the major cause for renal allograft failure. To identify specific microRNAs and their regulation involved in these processes, total RNA from blood cells of 16 kidney transplanted (KTx) patients with ABMR, stable graft function (SGF) and with T-cell mediated rejection (TCMR) was isolated. MicroRNA expression was determined by high-throughput sequencing. Differentially expressed candidate microRNAs were analyzed with RT-PCR in patients with SGF (n = 53), urinary tract infection (UTI) (n = 17), borderline rejection (BL) (n = 19), TCMR (n = 40), ABMR (n = 22) and IFTA (n = 30)...
2018: PloS One
Hamid Mazdak, Mojgan Ghavami, Shahaboddin Dolatkhah, Parnaz Daneshpajouhnejad, Mehdi Fesharakizadeh, Shahriar Fesharakizadeh, Abdolamir Atapour, Parvin Mahzouni, Mozaffar Hashemi, Roxana Salajegheh, Diana Taheri
Background: The aim of this study was to determine the pathologic causes of renal allograft failure in transplant nephrectomy specimens. Materials and Methods: In this cross-sectional study performed in the referral transplant center of Isfahan, Iran, medical files of all patients who underwent nephrectomy in 2008-2013 were studied. Age at transplantation, sex, donor's characteristics, causes of primary renal failure, duration of allograft function, and pathologic reasons of nephrectomy were extracted...
2018: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
Aravind Cherukuri, Rajil Mehta, Puneet Sood, Sundaram Hariharan
Early histological progression that associates with delayed graft function (DGF) and its relationship to graft outcomes is less well-understood. We systematically evaluated early acute and chronic histological changes associated with DGF through serial biopsies (protocol: 3 and 12 months; for-cause) and related them to graft outcomes. 56/294 (19.04%) of our patients had DGF. DGF was associated with a progressive increase in both Banff 't' and 'i' scores from 2 weeks to 3 and 12 months with a resultant increase in T cell mediated rejection (TCMR) that was significantly greater than those with primary graft function (PGF)...
July 14, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Shigeo Hara
The Banff histopathology classification system is the gold standard for assessing the causes of kidney allograft dysfunction triggered by antibody-mediated and T-cell-mediated immune reactions, thereby providing mechanistic insight and guiding therapeutic decisions. The original Banff classification (1993) consisted of four histological categories representing cell-mediated rejection: interstitial inflammation (i), tubulitis (t), endoarteritis (v), and transplant glomerulitis (g). The revised Banff 2007 classification added total inflammation score (ti) from both scarred and unscarred areas based on evolving interpretations of interstitial infiltrates...
July 2018: Nephrology
Michael McRae, François Bouchard-Boivin, Stéphanie Béland, Réal Noël, Isabelle Côté, Isabelle Lapointe, Julie Lesage, Eva Latulippe, Julie Riopel, Dominick Santoriello, Syed A Husain, Olivier Désy, Isabelle Houde, Ibrahim Batal, Sacha A De Serres
BACKGROUND: Since the borderline changes suspicious for acute T-cell-mediated rejection (BL) category was broadened, there has been a debate regarding the right threshold for tubulitis (t) and interstitial inflammation (i) scores. METHODS: We studied a first cohort of 111 patients with BL found on an indication biopsy between 2006 and 2016 and compared those with scores of t1i0 (BLt1i0) to those with higher scores (BL≥t1i1). A second cohort of 56 patients with BL was used for external validation...
June 18, 2018: Transplantation
Kyoung Woon Kim, Bo-Mi Kim, Kyoung Chan Doh, Mi-La Cho, Chul Woo Yang, Byung Ha Chung
The regulatory function of CCR7+ CD8+ T cells against effector T-cells involved in T-cell mediated rejection (TCMR) in kidney transplant recipients was investigated. In vitro experiments explored the ability of CCR7+ CD8+ T cells to suppress T-cell proliferation under T-cell activation conditions or during coculture with human renal proximal tubular epithelial cells (HRPTEpiC). In an ex vivo experiment, the proportion of CCR7+ /CD8+ , FOXP3+ /CCR7+ CD8+ T and effector T-cell subsets were compared between the normal biopsy control (NC, n = 17) and TCMR group (n = 17)...
June 11, 2018: Scientific Reports
Galina Severova-Andreevska, Ladislava Grcevska, Gordana Petrushevska, Koco Cakalaroski, Aleksandar Sikole, Olivera Stojceva-Taneva, Ilina Danilovska, Ninoslav Ivanovski
INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR)...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
Christine M Mincham, Ian W Gibson, Atul Sharma, Chris Wiebe, Rupasri Mandal, David Rush, Peter Nickerson, Julie Ho, David S Wishart, Tom D Blydt-Hansen
Urinary CXCL10 and metabolites are biomarkers independently associated with TCMR. We sought to test whether these biomarkers fluctuate in association with histological severity of TCMR over short time frames. Forty-nine pairs of renal biopsies obtained 1-3 months apart from 40 pediatric renal transplant recipients were each scored for TCMR acuity score (i + t; Banff criteria). Urinary CXCL10:Cr and TCMR MDS were obtained at each biopsy and were tested for association with changes between biopsies in acuity, estimated GFR (ΔeGFR), and 12-month ΔeGFR...
August 2018: Pediatric Transplantation
Brian J Nankivell, Chow H P'Ng, Jeremy R Chapman
Tubulitis without interstitial inflammation (Banff i0), termed "isolated tubulitis" (ISO-T), has been controversially included within the Banff "borderline" category of acute T cell mediated rejection (TCMR). This single-center, retrospective, observational study of 2055 consecutive biopsies from 775 recipients, determined the clinical significance of ISO-T. ISO-T prevalence was 19.1%, comprising mild tubulitis (i0t1) in 97.2%. Independent clinical predictors of tubulitis were HLA mismatch, prior TCMR and antibody-mediated rejection, pulse corticosteroids, and BKVAN (P = ...
April 24, 2018: American Journal of Transplantation
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