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Sandesh Parajuli, Didier A Mandelbrot, Brenda Muth, Maha Mohamed, Neetika Garg, Fahad Aziz, Robert R Redfield, Weixiong Zhong, Brad C Astor, Arjang Djamali
Background: There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation. Methods: In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks...
December 2017: Transplantation Direct
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G Nordestgaard, Ruth Frikke-Schmidt
BACKGROUND: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. METHODS: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS)...
March 14, 2018: BMC Medicine
Ahmed I Akl, Hussein A Sheashaa, Mona Abdel Rahim, Muhammed A El Hadedy, Ayman F Refaie
Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative...
March 9, 2018: Experimental and Clinical Transplantation
B Handan Özdemir, Alev Ok Atılgan, Eda Yılmaz Akçay, Gökçe Özdemir, Ebru Ayvazoğlu Soy, Aydıncan Akdur, Mehmet Haberal
OBJECTIVES: Thrombotic microangiopathy is a form of renal capillary injury possibly associated with calcineurin inhibitor toxicity, acute humoral rejection, infections, and recurrent diseases. Here, we examined its incidence in patients diagnosed with acute and chronic active humoral rejection, polyomavirus nephropathy, acute cellular rejection, and immunoglobulin A recurrence. MATERIALS AND METHODS: In total, 272 renal allograft recipients who met the inclusion criteria were reevaluated for presence of renal thrombotic microangiopathy...
March 2018: Experimental and Clinical Transplantation
M Vankalakunti, R Augustine, R Jangamani, V Siddini, R Bonu, K Babu, S H Ballal
Dense deposit disease (DDD), earlier called Type II membranoproliferative glomerulonephritis is distinct disease having frequent relapses reaching end-stage kidney disease by 10-year in up to 50%-60% of cases and high recurrence rate in the allograft. The term DDD is derived from its distinctive ribbon-like osmiophilic deposits in the lamina densa of glomerular basement membrane by electron microscopy. Pathogenetically, alternate pathway dysfunction leads to this disease, which is diagnosed by ultrastructure...
January 2018: Indian Journal of Nephrology
Francisco E Rodríguez Castellanos, Francisco Domínguez Quintana, Virgilia Soto Abraham, Eduardo Mancilla Urrea
INTRODUCTION: Kidney transplantation is considered the ideal treatment for end-stage renal disease. Acute rejection can influence graft survival. The aim of this study was to propose a classification system for acute rejection based on factor analysis. MATERIALS AND METHODS: Data were collected from kidney transplant recipients with acute rejection diagnosis based on standard histological variables, the presence of peritubular eosinophils, and immunolabeling for lysozyme and myeloperoxidase in kidney tissue...
March 2018: Iranian Journal of Kidney Diseases
Fei Hua, Yueqiu Chen, Ziying Yang, Xiaomei Teng, Haoyue Huang, Zhenya Shen
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) could exert a potent immunosuppressive effect, and therefore may have a therapeutic potential in T-cell-dependent pathologies. We aimed to examine the effects of BMSCs on immune tolerance of allogeneic heart transplantation and the involvement of CD45RB+ dendritic cells (DCs). METHODS: Bone marrow-derived DCs and BMSCs were co-cultured, with CD45RB expression on the surface of DCs measured by flow cytometry...
February 28, 2018: Clinical Transplantation
M L Arnold, A Kainz, L G Hidalgo, F Eskandary, N Kozakowski, M Wahrmann, H Haslacher, R Oberbauer, A Heilos, B M Spriewald, P F Halloran, G A Böhmig
Fc-dependent effector mechanisms may contribute to antibody-mediated rejection (ABMR), and distinct gene polymorphisms modifying the function of Fc gamma receptors (FcγR) may potentially influence the capability of donor-specific antibodies (DSA) to trigger inflammation. To evaluate the relevance of functional FcγR variants in late ABMR, 85 DSA-positive kidney allograft recipients, who were recruited upon antibody screening of 741 prevalent patients, were genotyped for polymorphisms in FcγRIIA (FCGR2A-H/R131 ; rs1801274), FcγRIIIA (FCGR3A-V/F158 ; rs396991) and FcγRIIIB [FCGR3B-neutrophil antigen 1 (NA1)/NA2; rs35139848]...
February 25, 2018: American Journal of Transplantation
H L Stevenson, M M Prats, K Isse, A Zeevi, Y Avitzur, V L Ng, A J Demetris
According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with co-existent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified 9 patients at a mean of 1,805 days post-transplantation and compared these to matched controls...
February 21, 2018: American Journal of Transplantation
Daniel Ajona, Marcin Okrój, María J Pajares, Jackeline Agorreta, María D Lozano, Javier J Zulueta, Carla Verri, Luca Roz, Gabriella Sozzi, Ugo Pastorino, Pierre P Massion, Luis M Montuenga, Anna M Blom, Ruben Pio
Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage samples from lung cancer patients and controls. In case-control studies, the area under the ROC curve for the diagnosis of lung cancer was 0...
January 19, 2018: Oncotarget
Lovelesh Kumar Nigam, Aruna V Vanikar, Kamal V Kanodia, Rashmi D Patel, Kamlesh S Suthar, Himanshu V Patel
Banff'13 update included C4d-antibody-mediated rejection (ABMR) as a separate entity responsible for graft dysfunction with limited clinical/prognostic implications. We present a retrospective study to determine the incidence and outcome of C4d-negative ABMR. A total of 987 renal allograft (RA) biopsies obtained from 987 RA recipients were studied from January 2013 to January 2016. All samples were subjected to light microscopy using standard stains and C4d immunohistochemistry on paraffin sections and reported according to modified Banff's criteria...
January 2018: Saudi Journal of Kidney Diseases and Transplantation
Marion Rabant, Maud Racapé, Laetitia-Marie Petit, Jean Luc Taupin, Olivier Aubert, Julie Bruneau, Patrick Barbet, Olivier Goulet, Christophe Chardot, Caroline Suberbielle, Florence Lacaille, Danielle Canioni, Jean-Paul Duong Van Huyen
The diagnostic criteria for antibody-mediated rejection (ABMR) after small bowel transplantation (SBT) are not clearly defined, although the presence of Donor Specific Antibodies (DSA) has been reported to be deleterious for graft survival. We aimed to determine the incidence and prognostic value of DSA and C4d in pediatric SBT and to identify the histopathological features associated with C4d positivity. We studied all intestinal biopsies (IBx) obtained in the first year post-transplantation (n=345) in a prospective cohort of 23 children...
February 3, 2018: American Journal of Transplantation
Shengye Zhang, Jane Shaw-Boden, Yara Banz, Anjan K Bongoni, Adriano Taddeo, Rolf Spirig, Marc W Nolte, Peter J Cowan, Robert Rieben
OBJECTIVE: Ischemia-reperfusion (I/R) injury is a major clinical problem linked to vascular surgery. Currently, no drugs to prevent or to treat I/R injury are approved for clinical use. C1 inhibitor (C1 INH) is known to reduce activation of the plasma cascade systems that are involved in the pathophysiologic process of I/R injury. The aim of this study was therefore to investigate the effect of C1 INH on complement deposition and endothelial cell activation in a rat model of hind limb I/R injury...
January 27, 2018: Journal of Vascular Surgery
Jan H von der Thüsen, Elly Vandermeulen, Robin Vos, Birgit Weynand, Erik K Verbeken, Stijn E Verleden
Chronic lung allograft dysfunction continues to be the main contributor to poor long-term allograft survival after lung transplantation. The restrictive phenotype of chronic lung allograft dysfunction carries a particularly poor prognosis. Little is known about the pathogenetic mechanisms involved in restrictive chronic lung allograft dysfunction. In this study, we performed histomorphological and immunohistochemical analysis of restrictive chronic lung allograft dysfunction lungs. Explant lung tissue from 21 restrictive chronic lung allograft dysfunction patients was collected and histopathologic patterns of rejection, fibrosis and vascular changes were scored after routine histochemical stains and additional immunohistochemistry for endothelial markers and C4d...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Fabiano Bichuette Custódio, Crislaine Aparecida da Silva, Fernanda Rodrigues Helmo, Juliana Reis Machado, Marlene Antônia Dos Reis
INTRODUCTION: Membranous nephropathy (MN) is one of the major causes of nephrotic syndrome. The complement system plays a key role in the pathophysiology of MN. OBJECTIVES: To identify the complement pathway possibly activated in MN cases and correlate the presence of C4d with more severe clinical and histological markers. METHODS: Sixty nine cases from renal biopsy with membranous nephropathy were investigated. The presence of C1q was analyzed by direct immunofluorescence; and expression of C4d by immunohistochemistry...
October 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
Mark Haas
PURPOSE OF REVIEW: To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. RECENT FINDINGS: The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR...
January 2, 2018: Current Opinion in Nephrology and Hypertension
Howard D Wang, Samuel A J Fidder, Devin T Miller, Georg J Furtmüller, Ali Reza Ahmadi, Felix Nägele, Joseph Lopez, Amy Quan, Joshua Budihardjo, Denver M Lough, Burcu Akpinarli, Joanna Etra, Dalibor Vasilic, Giorgio Raimondi, W P Andrew Lee, Robert A Montgomery, Zhaoli Sun, Gerald Brandacher
BACKGROUND: Candidates for vascularized composite allotransplantation (VCA) are frequently sensitized, putting them at risk for antibody-mediated rejection (AMR). Current desensitization strategies are imperfect and require a living-donor setting. Here we investigated the impact of sensitization on and the efficacy of a desensitization protocol utilizing syngeneic hematopoietic stem cell transplantation (HSCT) to prevent AMR in VCA. METHODS: Skin transplants from Dark Agouti (DA) to Lewis rats were performed for sensitization...
January 2, 2018: Transplantation
Neil Dah, Bellamy Co, M Smith, H Haga, Y Zen, M Sebagh, K Ruppert, J Lunz, S G Hübscher, A J Demetris
Discussion of liver antibody mediated rejection during the 2011, 2013 and 2015 Banff liver sessions raised concerns over reliability of complement fragment 4d (C4d) staining, precipitating a global survey followed by a tissue microarray staining quality assessment study among centers on formalin-fixed, paraffin-embedded tissue. Tissue microarray sections containing tissue plugs of resected native and allograft (with acute antibody mediated rejection) liver, heart and kidney (n=33 total cores) were sent to 31 centers for C4d staining using local method (s) and pathologist scoring...
December 26, 2017: Human Pathology
M Haas, A Loupy, C Lefaucheur, C Roufosse, D Glotz, D Seron, B J Nankivell, P F Halloran, R B Colvin, N Alachkar, S Bagnasco, Y Bouatou, J U Becker, L Cornell, J P Duong van Huyen, I Gibson, R Mannon, M Naesens, V Nickeleit, P Nickerson, D L Segev, H K Singh, M Stegall, P Randhawa, L Racusen, K Solez, M Mengel
The kidney sessions of the 2017 Banff Conference focused on two areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by two groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with under-immunosuppression...
December 15, 2017: American Journal of Transplantation
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