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https://www.readbyqxmd.com/read/28226404/the-effect-of-cortex-medulla-proportions-on-molecular-diagnoses-in-kidney-transplant-biopsies-rejection-and-injury-can-be-assessed-in-medulla
#1
Katelynn S Madill-Thomsen, Roger C Wiggins, Farsad Eskandary, Georg A Böhmig, Philip F Halloran
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28166393/donor-specific-antibodies-c1q-binding-improvement-in-kidney-graft-management
#2
Sylvie Ferrari-Lacraz
The diagnosis of acute antibody mediated rejection (ABMR) after kidney transplantation is based on three parameters: 1) decreased renal function, 2) histopathological signs of rejection, 3) presence of Donor Specific Antibody (DSA) [1]. Patient survival, as well as graft survival have improved since 5 to 10 years [2], thanks to several factors, including better management of patients, better immunosuppressive regimens, detection and avoidance of DSA. Although anti-HLA antibodies follow-up have improved ABMR management, its treatment remains challenging, and outcome may be worsened because of a delay in the diagnosis...
February 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28121909/urinary-metabolomics-for-noninvasive-detection-of-antibody-mediated-rejection-in-children-after-kidney-transplantation
#3
Tom D Blydt-Hansen, Atul Sharma, Ian W Gibson, David S Wishart, Rupasri Mandal, Julie Ho, Peter Nickerson, David Rush
BACKGROUND: Biomarkers are needed that identify patients with antibody-mediated rejection (ABMR). The goal of this study was to evaluate the utility of urinary metabolomics for early noninvasive detection of ABMR in pediatric kidney transplant recipients. METHODS: Urine samples (n=396) from a prospective, observational cohort of 59 renal transplant patients with surveillance or indication biopsies were assayed for 133 unique metabolites by quantitative mass spectrometry...
January 25, 2017: Transplantation
https://www.readbyqxmd.com/read/28114171/long-term-outcomes-of-kidney-transplantation-in-patients-with-high-levels-of-preformed-dsa-the-necker-high-risk-transplant-program
#4
Lucile Amrouche, Olivier Aubert, Caroline Suberbielle, Marion Rabant, Jean-Paul Duong Van Huyen, Frank Martinez, Rebecca Sberro-Soussan, Anne Scemla, Claire Tinel, Renaud Snanoudj, Julien Zuber, Ruy Cavalcanti, Marc-Olivier Timsit, Lionel Lamhaut, Dany Anglicheau, Alexandre Loupy, Christophe Legendre
BACKGROUND: There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (ABMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required. METHODS: Our high immunologic risk program included 95 patients with high peak or day-0 DSA levels (mean fluorescence intensity (MFI) > 3000) with a CDC negative crossmatch, who received a posttransplant desensitization protocol starting at day-0 with high-dose IVIg, plasma exchanges and eventually rituximab...
January 21, 2017: Transplantation
https://www.readbyqxmd.com/read/28104301/differences-in-pathologic-features-and-graft-outcomes-in-antibody-mediated-rejection-of-renal-allografts-due-to-persistent-recurrent-versus-de-novo-donor-specific-antibodies
#5
Mark Haas, James Mirocha, Nancy L Reinsmoen, Ashley A Vo, Jua Choi, Joseph M Kahwaji, Alice Peng, Rafael Villicana, Stanley C Jordan
Antibody-mediated rejection (ABMR) of renal allografts occurs in two forms. Type 1 ABMR results from persistence and/or a rebound of preexisting donor-specific antibodies in sensitized patients and usually occurs early post-transplantation. Type 2 ABMR is associated with de novo donor-specific antibodies and usually occurs over one year post-transplantation. It is generally accepted that types 1 and 2 also differ with regard to certain pathologic features including the frequencies of C4d positivity and concurrent cell-mediated rejection...
January 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28104146/successful-rescue-of-late-onset-antibody-mediated-rejection-12-years-after-living-donor-intestinal-transplantation-a-case-report
#6
G S Wu, Q C Zhao, Z S Li, Y Wu, W Z Wang, M B Li, H Shi, M Wang, D L Chen, J Y Zheng, X Wang, D M Fan
BACKGROUND: Antibody-mediated rejection (ABMR) has recently surfaced as a potential form of graft dysfunction after intestinal transplantation. METHODS: We present a case of an intestinal transplant recipient who developed late-onset ABMR 12 years after living-donor transplantation. An 18-year-old male recipient with a history of extensive intestinal resection secondary to acute bowel volvulus exhibited an excellent baseline immune profile for transplantation, including ABO-identical and HLA-haploidentical to the donor; a negative cross-match with a panel reactive antibody of 3...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28101959/comprehensive-analysis-of-transcript-changes-associated-with-allograft-rejection-combining-universal-and-selective-features
#7
Philip F Halloran, Jeffery M Venner, Konrad S Famulski
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated (TCMR) or antibody-mediated rejection (ABMR). We used eight class comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all non-rejecting biopsies, including other diseases. The universal algorithm, rejection vs...
January 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#8
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28009783/treatment-of-acute-antibody-mediated-renal-allograft-rejection-with-cyclophosphamide
#9
Johannes Waiser, Michael Duerr, Klemens Budde, Birgit Rudolph, Kaiyin Wu, Friederike Bachmann, Fabian Halleck, Constanze Schönemann, Nils Lachmann
BACKGROUND: Antibody-mediated rejection (ABMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated, whether cyclophosphamide combined with plasmapheresis (PPH) and intravenous immunoglobulins (IVIG) is an option for patients with ABMR. METHODS: Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute ABMR with i...
December 22, 2016: Transplantation
https://www.readbyqxmd.com/read/28005572/polyreactive-natural-antibodies-in-transplantation
#10
Emmanuel Zorn, Sarah B See
PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27909648/fc%C3%AE-receptors-in-solid-organ-transplantation
#11
REVIEW
Tomas Castro-Dopico, Menna R Clatworthy
In the current era, one of the major factors limiting graft survival is chronic antibody-mediated rejection (ABMR), whilst patient survival is impacted by the effects of immunosuppression on susceptibility to infection, malignancy and atherosclerosis. IgG antibodies play a role in all of these processes, and many of their cellular effects are mediated by Fc gamma receptors (FcγRs). These surface receptors are expressed by most immune cells, including B cells, natural killer cells, dendritic cells and macrophages...
2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/27906829/evidence-for-cd16a-mediated-nk-cell-stimulation-in-antibody-mediated-kidney-transplant-rejection
#12
Michael D Parkes, Philip F Halloran, Luis G Hidalgo
BACKGROUND: Natural killer (NK) cells localize in the microcirculation in antibody-mediated rejection (ABMR) and have been postulated to be activated by donor-specific anti-HLA antibodies triggering their CD16a Fc receptors. However, direct evidence for NK cell CD16a triggering in ABMR is lacking. We hypothesized that CD16a-inducible NK cell-selective transcripts would be expressed in human ABMR biopsies and would offer evidence for CD16a triggering. METHODS: We stimulated human NK cells through CD16a in vitro, characterized CD16a-inducible transcripts, and studied their expression in human kidney transplant biopsies with ABMR and in an extended human cell panel to determine their selectivity...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27888573/b-cell-activating-factor-baff-a-predictor-of-antibody-mediated-rejection-in-kidney-transplantation-recipients
#13
Wannarat Pongpirul, Wiwat Chancharoenthana, Krit Pongpirul, Asada Leelahavanichakul, Wipawee Kittikowit, Kamonwan Jutivorakool, Bunthoon Nonthasoot, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa, Natavudh Townamchai
BACKGROUND: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection...
November 26, 2016: Nephrology
https://www.readbyqxmd.com/read/27862883/the-banff-2015-kidney-meeting-report-current-challenges-in-rejection-classification-and-prospects-for-adopting-molecular-pathology
#14
A Loupy, M Haas, K Solez, L Racusen, D Glotz, D Seron, B J Nankivell, R B Colvin, M Afrouzian, E Akalin, N Alachkar, S Bagnasco, J U Becker, L Cornell, C Drachenberg, D Dragun, H de Kort, I W Gibson, E S Kraus, C Lefaucheur, C Legendre, H Liapis, T Muthukumar, V Nickeleit, B Orandi, W Park, M Rabant, P Randhawa, E F Reed, C Roufosse, S V Seshan, B Sis, H K Singh, C Schinstock, A Tambur, A Zeevi, M Mengel
The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies...
January 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27848058/current-pathological-perspectives-on-chronic-rejection-in-renal-allografts
#15
REVIEW
Shigeo Hara
Chronic rejection in renal transplantation clinically manifests as slow deterioration in allograft function and is a major contributor of late renal graft loss. Most cases of chronic rejection involve chronic antibody-mediated rejection (ABMR) triggered by the interaction of donor-specific alloantibodies with endothelial cells of the microcirculation. The evolution of the Banff classification involved a major revision of the ABMR criteria during the 2000s and led to the inclusion of detailed pathological characteristics of chronic ABMR in the 2013 Banff scheme, including microcirculation damage observed as newly formed basement membranes and arterial fibrous intimal proliferation...
November 16, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27822209/antibody-subclass-repertoire-and-graft-outcome-following-solid-organ-transplantation
#16
REVIEW
Nicole M Valenzuela, Michelle J Hickey, Elaine F Reed
Long-term outcomes in solid organ transplantation are constrained by the development of donor-specific alloantibodies (DSA) against human leukocyte antigen (HLA) and other targets, which elicit antibody-mediated rejection (ABMR). However, antibody-mediated graft injury represents a broad continuum, from extensive complement activation and tissue damage compromising the function of the transplanted organ, to histological manifestations of endothelial cell injury and mononuclear cell infiltration but without concurrent allograft dysfunction...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27818660/unraveling-the-role-of-allo-antibodies-and-transplant-injury
#17
REVIEW
Yoshiko Matsuda, Minnie M Sarwal
Alloimmunity driving rejection in the context of solid organ transplantation can be grossly divided into mechanisms predominantly driven by either T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), though the co-existence of both types of rejections can be seen in a variable number of sampled grafts. Acute TCMR can generally be well controlled by the establishment of effective immunosuppression (1, 2). Acute ABMR is a low frequency finding in the current era of blood group and HLA donor/recipient matching and the avoidance of engraftment in the context of high-titer, preformed donor-specific antibodies...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27788792/outcome-of-abo-incompatible-living-donor-renal-transplantations-a-single-center-experience-from-eastern-india
#18
D S Ray, S Thukral
BACKGROUND: With the incessantly increasing number of patients on the waiting list for renal transplants, crossing the blood group barrier can substantially increase the donor pool. We started ABO-incompatible (ABOi) renal transplantation in 2013 with a relatively low-cost preconditioning protocol (additional cost, ∼$1200). This study reports the short-term outcome of ABOi renal transplantations performed at our institution. METHODS: A total of 45 adult ABOi kidney transplant recipients (KTRs) were included in the study...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27693310/the-selective-biomarker-il-8-identifies-ifta-after-kidney-transplantation-in-blood-cells
#19
Mareen Matz, Christine Lorkowski, Katharina Fabritius, Kaiyin Wu, Birgit Rudolph, Stefan Frischbutter, Susanne Brakemeier, Jens Gaedeke, Hans-H Neumayer, Mir-Farzin Mashreghi, Klemens Budde
Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers in blood cells and serum may serve as diagnostic tools but studies with high patient numbers and differential groups are rare. We validated the potential value of several markers on mRNA level in blood cells and serum protein level in 166 samples from kidney transplanted patients under standard immunosuppressive therapy (steroids±mycophenolic acid±calcineurin inhibitor) with stable graft function, urinary tract infection (UTI), IFTA, antibody-mediated rejection (ABMR), and T-cell-mediated rejection (TCMR) applying RT-PCR and ELISA...
November 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27683635/updates-on-antibody-mediated-rejection-in-intestinal-transplantation
#20
REVIEW
Guo-Sheng Wu
Antibody-mediated rejection (ABMR) has increasingly emerged as an important cause of allograft loss after intestinal transplantation (ITx). Compelling evidence indicates that donor-specific antibodies can mediate and promote acute and chronic rejection after ITx. However, diagnostic criteria for ABMR after ITx have not been established yet and the mechanisms of antibody-mediated graft injury are not well-known. Effective approaches to prevent and treat ABMR are required to improve long-term outcomes of intestine recipients...
September 24, 2016: World Journal of Transplantation
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