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Antibody-mediated Rejection

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https://www.readbyqxmd.com/read/28640789/complement-mediated-enhancement-of-monocyte-adhesion-to-endothelial-cells-by-hla-antibodies-and-blockade-by-a-specific-inhibitor-of-the-classical-complement-cascade-tnt003
#1
Nicole M Valenzuela, Kimberly A Thomas, Arend Mulder, Graham C Parry, Sandip Panicker, Elaine F Reed
BACKGROUND: Antibody-mediated rejection (AMR) of most solid organs is characterized by evidence of complement activation and/or intragraft macrophages (C4d + and CD68+ biopsies). We previously demonstrated that crosslinking of HLA I by antibodies triggered endothelial activation and monocyte adhesion. We hypothesized that activation of the classical complement pathway at the endothelial cell surface by HLA antibodies would enhance monocyte adhesion through soluble split product generation, in parallel with direct endothelial activation downstream of HLA signaling...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28638610/looking-for-the-needle-in-the-kidney-transplantation-haystack
#2
Josep M Cruzado, Edoardo Melilli
The diagnosis of acute rejection still relies on renal allograft biopsy. In fact, histological features including C4d staining can be useful to differentiate cellular and antibody-mediated acute rejection. However, the pathogenic mechanism to define the type of rejection is usually assessed by anti-HLA donor specific antibodies (DSA) monitoring. Suspicion of acute rejection is usually based on renal function deterioration. This method has low sensitivity. Moreover, creatinine increase follows graft injury and therefore the diagnosis is performed when there is an ongoing acute rejection...
February 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28635356/simultaneous-abo-incompatible-living-donor-liver-transplantation-and-splenectomy-without-plasma-exchange-in-china-two-case-reports
#3
Guoyong Chen, Janjun Sun, Sidong Wei, Yongfeng Chen, Gaofeng Tang, Zhantao Xie, Huaen Xu, Janbin Chen, Huibo Zhao, Zhenhua Yuan, Weiwei Wang, Guangbo Liu, Bing Wang, Biao Niu
ABO-incompatible (ABO-i) living-donor liver transplantation (LDLT) is performed if an ABO-compatible graft cannot be obtained. However, a perfect desensitization protocol has not been established worldwide, especially for simultaneous ABO-i LDLT and splenectomy. We herein report two cases of ABO-i LDLT. To the best of our knowledge, this is the first case report of ABO-i LDLT in an adult patient in China. Splenectomy and T-cell-targeted immunosuppression (basiliximab) was used to overcome the blood group barrier in these recipients...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28634772/the-effect-of-desensitization-therapy-in-kidney-transplantation
#4
Yong Chul Kim, Mi-Yeon Yu, Jung Pyo Lee, Hajeong Lee, Sang-Il Min, Jongwon Ha, Yon Su Kim
BACKGROUND: Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear. METHODS: We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group...
June 20, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#5
Theodoros Eleftheriadis, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Triggered by the successful administration of the proteasome inhibitor bortezomib in kidney transplant recipients with acute or chronic antibody-mediated rejection, we evaluated the effect of the proteasome inhibitor CEP-18770 and of the selective immunoproteasome inhibitor ONX-0914 on cellular and humoral alloimmunity. Cellular alloimmunity was assessed by cell proliferation in a two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method, where humoral alloimmunity was induced in one-way MLR...
June 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28626871/a-successful-living-donor-liver-re-transplantation-for-graft-failure-within-seven-days-due-to-acute-de-novo-donor-specific-anti-hla-antibody-mediated-rejection
#6
Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Kiyotomo Abe, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Hiroshi Yagi, Naoki Shimojima, Masahiro Shinoda, Minoru Kitago, Hideaki Obara, Yasushi Fuchimoto, Kaori Kameyama, Yuko Kitagawa, Tatsuo Kuroda
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas...
June 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28624489/association-of-genetic-polymorphisms-of-macrophage-inhibitory-factor-mif-and-b-cell-activating-factor-baff-with-the-detection-of-donor-specific-antibodies-in-kidney-allograft-recipients
#7
Youngil Chang, Tariq Shah, David I Min
The posttransplant development of donor specific antibodies (DSA) initiates the antibody mediated rejection (AMR), which is associated with the increased rate of graft loss. One of the characteristics of AMR is the infiltration of innate immune system including macrophages, monocytes, neutrophils or NK cells. Macrophage inhibitory factor (MIF) and B-cell activating factor (BAFF) are well known cytokines that are associated with the activation of the innate immune system which can damage kidney allograft. In this article, the association of the genetic polymorphisms of MIF and BAFF with the development of DSA including Class I and II in kidney transplant patients is investigated...
June 14, 2017: Human Immunology
https://www.readbyqxmd.com/read/28624139/applying-rigor-and-reproducibility-standards-to-assay-donor-derived-cell-free-dna-as-a-non-invasive-method-for-detection-of-acute-rejection-and-graft-injury-after-heart-transplantation
#8
Sean Agbor-Enoh, Ilker Tunc, Iwijn De Vlaminck, Ulgen Fideli, Andrew Davis, Karen Cuttin, Kenneth Bhatti, Argit Marishta, Michael A Solomon, Annette Jackson, Grace Graninger, Bonnie Harper, Helen Luikart, Jennifer Wylie, Xujing Wang, Gerald Berry, Charles Marboe, Kiran Khush, Jun Zhu, Hannah Valantine
BACKGROUND: Use of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts...
May 20, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28620559/ivig-associated-aseptic-meningitis-in-a-renal-transplant-patient
#9
Tamara Wanigasekera, Rachel J Grainger, Donal J Sexton, Colm Magee
The management of antibody-mediated rejection in renal transplant recipients involves plasmapheresis with IVIG. Aseptic meningitis is a rare adverse effect of IVIG therapy and is a diagnosis of exclusion. We report a case of a renal transplant patient who developed IVIG associated aseptic meningitis in the context of management of antibody-mediated rejection, four years after transplantation.
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28614805/assessing-rejection-related-disease-in-kidney-transplant-biopsies-based-on-archetypal-analysis-of-molecular-phenotypes
#10
Jeff Reeve, Georg A Böhmig, Farsad Eskandary, Gunilla Einecke, Carmen Lefaucheur, Alexandre Loupy, Philip F Halloran
Conventional histologic diagnosis of rejection in kidney transplants has limited repeatability due to its inherent requirement for subjective assessment of lesions, in a rule-based system that does not acknowledge diagnostic uncertainty. Molecular phenotyping affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems and quantify levels of uncertainty. Microarray data from 1,208 kidney transplant biopsies were collected prospectively from 13 centers...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28614703/circulating-angiotensin-type-ii-receptor-possible-marker-for-antibody-mediated-rejection-after-renal-transplantation
#11
Pamela M Kimball, Gaurav Gupta, Felecia McDougan
BACKGROUND: Presence of antibody[Ab] against angiotensin receptor[AT1R] indicates heightened risk for antibody mediated rejection[AMR] after transplantation but is insufficient as a marker. We speculated AT1R might be released systemically because of AMR and might be a useful biomarker. METHODS: AT1R was measured in blood from 73 Normals and 72 renal patients pre- and post-transplantation. Patients were stratified as AMR-free[Gp1], AMR<1yr[Gp2] and AMR>1yr[Gp3]...
June 11, 2017: Human Immunology
https://www.readbyqxmd.com/read/28611987/complement-in-kidney-transplantation
#12
REVIEW
Marek Cernoch, Ondrej Viklicky
The complement system is considered to be an important part of innate immune system with a significant role in inflammation processes. The activation can occur through classical, alternative, or lectin pathway, resulting in the creation of anaphylatoxins C3a and C5a, possessing a vast spectrum of immune functions, and the assembly of terminal complement cascade, capable of direct cell lysis. The activation processes are tightly regulated; inappropriate activation of the complement cascade plays a significant role in many renal diseases including organ transplantation...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28606879/can-immunosuppression-be-stopped-after-liver-transplantation
#13
REVIEW
Pierre-Alain Clavien, Xavier Muller, Michelle L de Oliveira, Philipp Dutkowski, Alberto Sanchez-Fueyo
Liver transplantation has improved dramatically over the past three decades, mainly as a result of advances in surgical techniques and management of post-transplant complications. The focus has now turned towards rescuing additional organs in the face of scarce organ supply, or prevention of long-term toxicity associated with immunosuppression. The liver appears to be privileged in terms of immune tolerance, with a low incidence of antibody-mediated rejection, which is in sharp contrast to other solid organ transplants, such as kidney, lung, and heart transplants...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28604987/iatrogenic-lymphocutaneous-fistula-secondary-to-right-sided-pheresis-catheter-placement-and-its-percutaneous-treatment-a-case-report
#14
Keith B Quencer, Raj R Ayyagari, Tamir Friedman
We present a case of an iatrogenic lymphocutaneous fistula secondary to placement of a tunneled, large bore (14.5 Fr) right-sided internal jugular vein for plasmapheresis to treat antibody-mediated kidney transplant rejection. While iatrogenic lymphatic leaks caused by neck and thoracic surgeries are well described in the literature, lymphatic leak or lymphocutaneous fistula resulting from image-guided placement of a central venous catheter through the right internal jugular vein has yet to be described. We also describe the successful percutaneous treatment of this lymphocutaneous fistula using a combination of n-butyl cyanoacrylate glue and embolization coils...
June 6, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28604384/antibody-mediated-rejection-across-solid-organ-transplants-manifestations-mechanisms-and-therapies
#15
Nicole M Valenzuela, Elaine F Reed
Solid organ transplantation is a curative therapy for hundreds of thousands of patients with end-stage organ failure. However, long-term outcomes have not improved, and nearly half of transplant recipients will lose their allografts by 10 years after transplant. One of the major challenges facing clinical transplantation is antibody-mediated rejection (AMR) caused by anti-donor HLA antibodies. AMR is highly associated with graft loss, but unfortunately there are few efficacious therapies to prevent and reverse AMR...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28601127/increase-in-spot-urine-protein-excretion-is-associated-with-late-kidney-graft-rejection-and-predicts-rejection-phenotype
#16
Miha Arnol, Manca Oblak, Gregor Mlinšek, Jelka Lindič, Aljoša Kandus, Dušan Ferluga, Nika Kojc, Jadranka Buturović-Ponikvar
AIMS: A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. METHODS: 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%)...
June 9, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28594750/blockade-of-hla-antibody-triggered-classical-complement-activation-in-sera-from-subjects-dosed-with-the-anti-c1s-monoclonal-antibody-tnt009-results-from-a-randomized-first-in-human-phase-1-trial
#17
Jakob Mühlbacher, Bernd Jilma, Markus Wahrmann, Johann Bartko, Farsad Eskandary, Christian Schörgenhofer, Michael Schwameis, Graham C Parry, James C Gilbert, Sandip Panicker, Georg A Böhmig
BACKGROUND: Complement may play a key role in antibody-mediated rejection (ABMR). A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. METHODS: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n=48; 7 consecutive cohorts: 0...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28594748/inhibition-of-spleen-tyrosine-kinase-reduces-renal-allograft-injury-in-a-rat-model-of-acute-antibody-mediated-rejection-in-sensitized-recipients
#18
Sharmila Ramessur Chandran, Yingjie Han, Greg H Tesch, Julie Di Paolo, William R Mulley, John Kanellis, Frank Y Ma, David J Nikolic-Paterson
BACKGROUND: Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signalling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. METHODS: Recipient Lewis rats (RT1) were immunized with donor (Dark Agouti, RT1) spleen cells (day -5)...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28590948/proximal-blockade-of-complement-a-neoclassical-approach-to-prevent-antibody-mediated-rejection
#19
Natalie A O'Neill, Richard N Pierson
No abstract text is available yet for this article.
June 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28583566/influences-of-pre-formed-donor-specific-anti-human-leukocyte-antigen-antibodies-in-living-donor-renal-transplantation-results-with-graft-immunocomplex-capture-fluorescence-analysis
#20
T Nakamura, H Ushigome, K Watabe, Y Imanishi, K Masuda, T Matsuyama, S Harada, K Koshino, T Iida, S Nobori, N Yoshimura
BACKGROUND: Advances in immunosuppressants enable organ transplantation for sensitized patients. However, influences of pre-formed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have not been fully understood in renal transplantation (RT). On the other hand, immunocomplex capture fluorescence analysis (ICFA) is a reliable method to detect donor-specific anti-HLA antibodies and HLA antigen complexes. Graft ICFA can detect DSA in an allograft (g-DSA). METHODS: To elucidate the consequences of pre-formed DSA, 198 patients who underwent living-donor RT were enrolled for this study (observation period: 57...
June 2017: Transplantation Proceedings
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