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https://www.readbyqxmd.com/read/29159992/clinical-and-histopathologic-features-of-antibody-mediated-rejection-among-pediatric-renal-transplant-recipients-with-preformed-vs-de-novo-donor-specific-antibodies
#1
Justin A Steggerda, Irene K Kim, Mark Haas, Xiaohai Zhang, Alexis Kang, Helen Pizzo, Elaine Kamil, Stanley Jordan, Dechu Puliyanda
Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy-proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow-up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA...
December 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29151252/dominant-c3-glomerulopathy-new-roles-for-an-old-actor-in-renal-pathology
#2
REVIEW
Nicola Pirozzi, Antonella Stoppacciaro, Paolo Menè
Recently, a number of reports have described dominant C3 deposits in renal biopsies of patients with infection-related glomerulonephritis (GN). While acute post-infectious GN and membranoproliferative GN are commonly characterized by immune deposits containing C3 and/or C4, the absence of immunoglobulin (Ig) and/or immune complexes at light or electron microscopy is a rather unusual observation. Dominant C3 deposition is believed to result from the alternative pathway of complement activation via the C3bBb "tickover" convertase...
November 18, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/29146701/mesangial-c4d-deposits-in-early-iga-nephropathy
#3
Alfons Segarra, Katheryne Romero, Irene Agraz, Natalia Ramos, Alvaro Madrid, Clara Carnicer, Elias Jatem, Ramón Vilalta, Luis Enrique Lara, Elena Ostos, Naiara Valtierra, Juliana Jaramillo, Karla V Arredondo, Gema Ariceta, Cristina Martinez
BACKGROUND AND OBJECTIVES: The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005...
November 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29135832/prognostic-value-of-the-persistence-of-c1q-binding-anti-hla-antibodies-in-acute-antibody-mediated-rejection-in-kidney-transplantation
#4
Elodie Bailly, Dany Anglicheau, Gilles Blancho, Philippe Gatault, Vincent Vuiblet, Valérie Chatelet, Emmanuel Morelon, Paolo Malvezzi, Anne Parissiadis, Jérôme Tourret, Gwendaline Guidicelli, Johnny Sayegh, Christiane Mousson, Philippe Grimbert, Isabelle Top, Moglie Le Quintrec, Raj Purgus, Pierre François Westeel, Barbara Proust, Valérie Chabot, Yvon Lebranchu, Frédéric Dehaut, Matthias Büchler
BACKGROUND: The differential pathogenicity of anti-HLA donor-specific antibodies (DSAs) is not fully understood. The presence of complement-binding DSAs help better defining the prognosis of acute antibody-mediated rejection (ABMR). The evolution of these antibodies after the treatment of ABMR is unknown. METHODS: We included patients from the French multicenter RITUX ERAH study diagnosed with acute antibody-mediated rejection (ABMR) within the first year of renal transplantation, with circulating anti-HLA DSAs and treated randomly by rituximab or placebo (and intravenous immunoglobulins, plasma exchange)...
November 13, 2017: Transplantation
https://www.readbyqxmd.com/read/29119152/quantitative-characterisation-of-conductive-fibers-by-capacitive-coupling
#5
Andres Ruland, Rouhollah Jalili, Attila J Mozer, Gordon G Wallace
This work presents a study on a capacitively coupled contactless conductivity detector (C4D) for micron-sized fibers. Following a previous report on the qualitative application of C4D for fibers, the present study provides a thorough analysis of the signal response to fiber conductivity. Using reduced graphene oxide (RGO) fibers, the detector response as a function of fiber length, cross-sectional area and resistance has been investigated. To study the effect of insulating coatings, Parylene-coated RGO fibers were also investigated...
November 9, 2017: Analyst
https://www.readbyqxmd.com/read/29119007/endothelial-dysfunction-is-associated-with-activation-of-the-type-i-interferon-system-and-platelets-in-patients-with-systemic-lupus-erythematosus
#6
Helena Tydén, Christian Lood, Birgitta Gullstrand, Christoffer Tandrup Nielsen, Niels H H Heegaard, Robin Kahn, Andreas Jönsen, Anders A Bengtsson
Objectives: Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods: We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs)...
2017: RMD Open
https://www.readbyqxmd.com/read/29108580/development-of-flow-systems-incorporating-membraneless-vaporization-units-and-flow-through-contactless-conductivity-detector-for-determination-of-dissolved-ammonium-and-sulfide-in-canal-water
#7
Waleed Alahmad, Thanakorn Pluangklang, Thitirat Mantim, Victor Cerdà, Prapin Wilairat, Nuanlaor Ratanawimarnwong, Duangjai Nacapricha
Use of membraneless vaporization (MBL-VP) unit with two cone-shaped reservoirs is presented for on-line separation and detection of non-volatile species. A flow system comprising two sets of MBL-VP units with a single in-house capacitively coupled contactless conductivity detector (C4D) was developed for dual determination of ammonium and sulfide ions. Using the continuous-flow section, two zones (280μL) of a sample, either mixed with sodium hydroxide (for ammonium) or hydrochloric acid (for sulfide), are separately delivered into the donor reservoir of the MBL-VP units...
January 15, 2018: Talanta
https://www.readbyqxmd.com/read/29064269/complement-activation-products-in-acute-heart-failure-potential-role-in-pathophysiology-responses-to-treatment-and-impacts-on-long-term-survival
#8
Marten Trendelenburg, Fabio Stallone, Kateryna Pershyna, Timo Eisenhut, Raphael Twerenbold, Karin Wildi, Denise Dubler, Lucia Schirmbeck, Christian Puelacher, Maria Rubini Gimenez, Zaid Sabti, Luca Osswald, Tobias Breidthardt, Christian Müller
BACKGROUND: Previous studies have indicated a correlation between heart failure, inflammation and poorer outcome. However, the pathogenesis and role of inflammation in acute heart failure (AHF) is incompletely studied and understood. The aim of our study was to explore the potential role of innate immunity - quantified by complement activation products (CAPs) - in pathophysiology, responses to treatment and impacts on long-term survival in AHF. METHODS: In a prospective study enrolling 179 unselected patients with AHF, plasma concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the first day of hospitalisation and prior to discharge...
February 1, 2017: European Heart Journal. Acute Cardiovascular Care
https://www.readbyqxmd.com/read/29025249/the-utility-of-glomerular-c4d-immunostaining-in-renal-biopsies-in-patients-with-immunoglobulin-a-nephropathy-a-clinicopathological-study
#9
Małgorzata Wągrowska-Danilewicz, Marian Danilewicz
The course of IgA nephropathy (IgAN) is highly variable and ranges from a totally benign condition to end-stage renal disease in approximately one third of cases. The identification of new prognostic markers could provide insights into the pathogenesis of IgAN and unveil new therapeutic avenues. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. It is thought that activation of the lectin pathway in IgAN is associated with more severe renal damage, and more severe histological findings...
2017: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
https://www.readbyqxmd.com/read/28992372/the-role-of-c4d-deposition-in-the-diagnosis-of-antibody-mediated-rejection-after-lung-transplantation
#10
P R Aguilar, D Carpenter, J Ritter, R D Yusen, C A Witt, D E Byers, T Mohanakumar, D Kreisel, E P Trulock, R R Hachem
Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs...
October 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28988608/routine-c4d-immunohistochemistry-in-cardiac-allografts-long-term-outcomes
#11
Aliya N Husain, Kamran M Mirza, Savitri E Fedson
BACKGROUND: In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death...
September 14, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28980446/anti-c1s-monoclonal-antibody-bivv009-in-late-antibody-mediated-kidney-allograft-rejection-results-from-a-first-in-patient-phase-1-trial
#12
F Eskandary, B Jilma, J Mühlbacher, M Wahrmann, H Regele, N Kozakowski, C Firbas, S Panicker, G C Parry, J C Gilbert, P F Halloran, G A Böhmig
The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of four weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years post-transplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA)...
October 5, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28970687/detection-of-t-and-b-cells-specific-complement-fixing-alloantibodies-using-flow-cytometry-a-diagnostic-approach-for-a-resource-limited-laboratory
#13
Dharmendra Jain, Pranav Dorwal, Amit Pande, Neetu Tyagi, Simmi Mehra, Vimarsh Raina
BACKGROUND AND OBJECTIVES: Various methods have been reported for the detection of antibodies in recipient sera, which can be human leukocyte antigens (HLAs) or non-HLA specific, complement- or noncomplement fixing, as well as donor T (HLA-Class-I) and/or B cell (HLA-Class-I and II) specific. These alloantibodies play a pivotal role in antibody-mediated renal transplantation rejection. Deposition of C4d in peritubular capillaries of a kidney biopsy is a marker of antibody-mediated rejection...
July 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28957430/shared-genetic-risk-between-migraine-and-coronary-artery-disease-a-genome-wide-analysis-of-common-variants
#14
Bendik S Winsvold, Francesco Bettella, Aree Witoelar, Verneri Anttila, Padhraig Gormley, Tobias Kurth, Gisela M Terwindt, Tobias M Freilinger, Oleksander Frei, Alexey Shadrin, Yunpeng Wang, Anders M Dale, Arn M J M van den Maagdenberg, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Ole A Andreassen, John-Anker Zwart
Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls)...
2017: PloS One
https://www.readbyqxmd.com/read/28954590/tubular-basement-membrane-immune-complex-deposition-is-associated-with-activity-and-progression-of-lupus-nephritis-a-large-multicenter-chinese-study
#15
H Wang, J Xu, X Zhang, Y L Ren, M Cheng, Z L Guo, J C Zhang, H Cheng, G L Xing, S X Wang, F Yu, M H Zhao
Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28945205/post-transplant-recurrent-bile-salt-export-pump-disease-a-form-of-antibody-mediated-graft-dysfunction-and-utilization-of-c4d
#16
Kalyani R Patel, Sanjiv Harpavat, Milton Finegold, Karen Eldin, John Hicks, Mihail Firan, Verena Keitel, Ralf Kubitz, Hao Wu
Recurrent bile salt export pump (rBSEP) disease has been reported in progressive familial intrahepatic cholestasis type 2 (PFIC2) patients following liver transplantation (LT) and is often refractory to standard anti-cellular rejection immunosuppressants. The mechanism of rBSEP disease is proposed to be a form of type II hypersensitivity reaction with de novo anti-BSEP antibodies blocking the function of allograft BSEP. Utilization of C4d has not been evaluated in rBSEP. We describe a girl with 3 episodes of rBSEP with severe pruritus at 8...
October 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28933341/c4d-expressing-glomerulopathy-and-proteinuria-post-transplantation-of-a-%C3%A2-too-big-for-size-mismatched-kidney-allograft-an-unusual-case-with-good-outcome%C3%A2
#17
Francois Gougeon, Alexei V Mikhailov, Keisha Gibson, Tomasz Kozlowski, Harsharan K Singh, Volker Nickeleit
A 5-year-old severely growth-retarded child with tubulointerstitial, oliguric end-stage renal disease received an adult-size kidney transplant. Three years post grafting under standard triple immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) de novo nephrotic range proteinuria without the nephrotic syndrome developed. Graft function was normal (serum creatinine: 0.2 - 0.3 mg/dL), there were no donor-specific HLA antibodies (DSA), and the urine sediment was inactive. Two biopsies collected 3 and 4 years post-transplantation showed severe glomerular capillary wall remodeling and associated pseudolinear C4d staining as morphologic correlates for the proteinuria...
September 21, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28918487/clinical-risk-stratification-of-paediatric-renal-transplant-recipients-using-c1q-and-c3d-fixing-of-de-novo-donor-specific-antibodies
#18
Jon Jin Kim, Olivia Shaw, Chloe Martin, George Michaelides, Ramnath Balasubramaniam, Neil J Sebire, Nizam Mamode, Anthony Dorling, Robert Vaughan, Stephen D Marks
INTRODUCTION: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. METHODS: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the Kaplan-Meier estimator...
September 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28882367/defining-the-phenotype-of-antibody-mediated-rejection-in-kidney-transplantation-advances-in-diagnosis-of-antibody-injury
#19
REVIEW
Neetika Garg, Milagros D Samaniego, Dana Clark, Arjang Djamali
The diagnostic criteria for antibody-mediated rejection (ABMR) are constantly evolving in light of the evidence. Inclusion of C4d-negative ABMR has been one of the major advances in the Banff Classification in recent years. Currently Banff 2015 classification requires evidence of donor specific antibodies (DSA), interaction between DSA and the endothelium, and acute tissue injury (in the form of microvasculature injury (MVI); acute thrombotic microangiopathy; or acute tubular injury in the absence of other apparent cause)...
August 15, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28881045/diagnostic-accuracy-of-immunofluorescence-versus-immunoperoxidase-staining-to-distinguish-immune-complex-mediated-glomerulonephritis-and-c3-dominant-glomerulopathy
#20
Yassine Bouatou, Jesper Kers, Marie S N Chevalier-Florquin, Nike Claessen, Tri Q Nguyen, Jeffrey Damman, Henrique Proença, Joris J T H Roelofs, Sandrine Florquin
AIMS: Membranoproliferative glomerulonephritis (MPGN) has been reclassified from an electron microscopy to an immunofluorescence (IF) based semi quantitative classification with immunoperoxidase (IP) technique as a backup option when IF is not possible. However, no data are available on the interobserver variability, the correlation and the reclassification of MPGN based on these two techniques. METHODS & RESULTS: We retrospectively analyzed cases of type 1 MPGN...
September 7, 2017: Histopathology
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