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Chronic antibody rejection

Yihung Huang, Evan Farkash
As both T cell and antibody-mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody-mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy...
September 2016: Advances in Chronic Kidney Disease
Cyril Garrouste, Dany Anglicheau, Nassim Kamar, Claire Bachelier, Joseph Rivalan, Bruno Pereira, Sophie Caillard, Julien Aniort, Philippe Gatault, Martin Soubrier, Johnny Sayegh, Charlotte Colosio, Anthony Buisson, Eric Thervet, Nicolas Bouvier, Anne Elisabeth Heng
Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1)...
October 2016: Medicine (Baltimore)
Arnaud Del Bello, Marie Danjoux, Nicolas Congy-Jolivet, Laurence Lavayssière, Laure Esposito, Fabrice Muscari, Nassim Kamar
BACKGROUND AND AIM: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. METHOD: Herein, we describe 9 cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. RESULTS: Two patients presented with aAMR at 10...
October 14, 2016: Journal of Gastroenterology and Hepatology
Priya Verghese, Kristen Gillingham, Arthur Matas, Srinath Chinnakotla, Blanche Chavers
The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months...
October 6, 2016: Pediatric Transplantation
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
Sourabh Chand, David Atkinson, Clare Collins, David Briggs, Simon Ball, Adnan Sharif, Kassiani Skordilis, Bindu Vydianath, Desley Neil, Richard Borrows
BACKGROUND: Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS: We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS: The spectrum of graft failure changed markedly depending on the timing of allograft failure...
2016: PloS One
Takeshi Maehana, Toshiaki Tanaka, Hiroshi Kitamura, Nobuyuki Fukuzawa, Hideki Ishida, Hiroshi Harada, Kazunari Tanabe, Naoya Masumori
BACKGROUND: Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation...
2016: PloS One
Marc K Halushka, Richard N Mitchell, Robert F Padera
Heart failure, whether acute or chronic, remains a major health care crisis affecting almost 6 million Americans and over 23 million people worldwide. Roughly half of those affected will die within 5 years, and the annual cost exceeds $30 billion in the US alone. Although medical therapy has made some modest inroads in partially stemming the heart failure tsunami, there remains a significant population for whom medication is unsuccessful or has ceased being effective; such patients can benefit from heart transplantation or mechanical circulatory support...
August 29, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Saskia Herz, Thomas Höfer, Matina Papapanagiotou, Julia Christina Leyh, Sarah Meyenburg, Dirk Schadendorf, Selma Ugurel, Alexander Roesch, Elisabeth Livingstone, Bastian Schilling, Cindy Franklin
BACKGROUND: Immune-checkpoint inhibitors have been approved for the treatment of metastatic melanoma based on several phase III trials. Patients after organ transplantation and patients with impaired renal function were excluded from these studies. Recently, allograft rejections were reported in organ transplant recipients receiving PD-1 blocking antibodies. PATIENTS AND FINDINGS: Four patients with metastatic melanoma and impaired kidney function (baseline serum creatinine 1...
November 2016: European Journal of Cancer
Undine Ariane Gerlach, Maren Klöpfel, Georgi Atanasov, Dietrich Polenz, Katrin Vogt, Stefanie Ahrlich, Marion Marksteiner, Anke Jurisch, Christoph Loddenkemper, Anja Reutzel-Selke, Birgit Sawitzki, Andreas Pascher
BACKGROUND: The pathology and diagnosis of acute and chronic rejection in intestinal transplantation are far from being completely understood. We established models of acute and chronic intestinal graft rejection and analysed peripheral and intragraft immune responses. METHODS: We performed intestinal transplantation (ITX) from Dark Agouti into Lewis rats applying single-dose tacrolimus (TAC) at varying concentrations. Graft histology and immunohistology were assessed on POD7,14,45...
September 8, 2016: Transplantation
Deján Dobi, Zsolt Bodó, Éva Kemény, László Bidiga, Zoltán Hódi, Pál Szenohradszky, Edit Szederkényi, Anikó Szilvási, Béla Iványi
The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3)...
September 7, 2016: Virchows Archiv: An International Journal of Pathology
Carlos Arias-Cabrales, Dolores Redondo-Pachón, María José Pérez-Sáez, Javier Gimeno, Ignacio Sánchez-Güerri, Sheila Bermejo, Adriana Sierra, Carla Burballa, Marisa Mir, Marta Crespo, Julio Pascual
INTRODUCTION: The impact of acute rejection in kidney graft survival is well known, but the prognosis of other diagnoses is uncertain. We evaluated the frequency and impact on graft survival of different diagnostic categories according to the Banff 2013 classification in a cohort of renal transplant recipients. MATERIAL AND METHODS: Retrospective study of 495 renal biopsies by indication in 322 patients from 1990-2014. Two independent observers reviewed the histological reports, reclassifying according to the Banff 2013 classification...
August 29, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Jamie Koo, David W Dawson, Sarah Dry, Samuel W French, Bita V Naini, Hanlin L Wang
In this study, we sought to determine the incidence of posttransplant complications including acute cellular rejection (ACR), infection, and posttransplant lymphoproliferative disease (PTLD) in mucosal allograft biopsies in patients with small bowel transplant at our institution. We retrospectively reviewed pathology reports from 5675 small bowel allograft biopsies from 99 patients and analyzed the following: indications for biopsy, frequency and grade of ACR, presence of infectious agents, results of work-up for potential PTLD, results of C4d immunohistochemistry (IHC), features of chronic mucosal injury, and findings in concurrent native bowel biopsies...
September 1, 2016: Clinical Transplantation
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
Elly Vandermeulen, Stijn E Verleden, Hannelore Bellon, David Ruttens, Elise Lammertyn, Sandra Claes, Jennifer Vandooren, Estafania Ugarte-Berzal, Dominique Schols, Marie-Paule Emonds, Dirk E Van Raemdonck, Ghislain Opdenakker, Geert M Verleden, Robin Vos, Bart M Vanaudenaerde
BACKGROUND: Recently, antibody mediated rejection (AMR) has been associated with a higher incidence of chronic lung allograft dysfunction (CLAD) and mortality after lung transplantation (LTx). We investigated markers related to AMR and matrix remodeling in CLAD, with special attention for its two phenotypes being bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD). METHODS: Immunoglobulins (IgA, IgE, IgG1-IgG4, total IgG and IgM) and complement (C4d and C1q) were quantified in lung lavage samples at the moment of BOS (n=15) or RAS (n=16) diagnosis; and were compared to stable transplant patients who served as control (n=14)...
September 2016: Transplant Immunology
Kaori Hanaoka, Yuka Kawato, Kaori Kubo, Tomonori Nakanishi, Masashi Maeda, Koji Nakamura, Jun Hirose, Takahisa Noto, Hidehiko Fukahori, Akihiko Fujikawa, Sosuke Miyoshi, Shoji Takakura, Tatsuaki Morokata, Yasuyuki Higashi
BACKGROUND: The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes (MHCs) are critical discrepancies. Here, we established a rat model of chronic rejection using fully MHC-mismatched strains in which kidney disease progresses even under immunosuppressive therapy...
September 2016: Transplant Immunology
Yasuyuki Nakada, Izumi Yamamoto, Shigeru Horita, Akimitsu Kobayashi, Aki Mafune, Haruki Katsumata, Takafumi Yamakawa, Ai Katsuma, Mayuko Kawabe, Yudo Tanno, Ichiro Ohkido, Nobuo Tsuboi, Hiroyasu Yamamoto, Masayoshi Okumi, Hideki Ishida, Takashi Yokoo, Kazunari Tanabe
The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection (CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts (ENDATs). We previously showed that the ENDAT caveolin-1 (CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients...
August 20, 2016: Clinical Transplantation
Annemarie Weissenbacher, Alexandre Loupy, Anil Chandraker, Stefan Schneeberger
PURPOSE OF REVIEW: The presence of donor-specific antibodies (DSA) increases the risk of graft failure. Although DSA characteristics, human leukocyte antigen class specificity, mean fluorescence intensity and immunoglobulin G subclasses, and their impact on the graft are quite well studied in solid organ transplants, very little information is known about their impact on vascularized composite allotransplantation (VCA). The aim of this review is to highlight recent publications regarding occurrence and effects of DSA, their follow-up and treatment in the field of VCA...
October 2016: Current Opinion in Organ Transplantation
Katrin Deiser, Diana Stoycheva, Ute Bank, Thomas Blankenstein, Thomas Schüler
The adoptive transfer of antigen-specific CD8+ T cells is a promising approach for the treatment of chronic viral and malignant diseases. In order to improve adoptive T cell therapy (ATT) of cancer, recent strategies aim at the antibody-based blockade of immunosuppressive signaling pathways in CD8+ T cells. Alternatively, adjuvant effects of immunostimulatory cytokines might be exploited to improve therapeutic CD8+ T cell responses. For example, Interleukin-7 (IL-7) is a potent growth, activation and survival factor for CD8+ T cells that can be used to improve virus- and tumor-specific CD8+ T cell responses...
2016: PloS One
J Rashidi-Alavijeh, A Heinold, K Willuweit, H A Baba, P A Horn, A Paul, O Witzke, G Gerken, K Herzer
BACKGROUND: Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins. METHODS: Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay...
July 2016: Zeitschrift Für Gastroenterologie
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