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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/28637898/activation-of-complement-by-pigment-epithelium-derived-factor-in-rheumatoid-arthritis
#3
Leonie M Vogt, Simone Talens, Ewa Kwasniewicz, Carsten Scavenius, André Struglics, Jan J Enghild, Tore Saxne, Anna M Blom
The aim of this study was to identify molecules that trigger complement activation in rheumatic joints. C4d, the final cleavage product of C4 activation, is found in the diseased joint and can bind covalently to complement-activating molecules. By using a highly specific Ab against a cleavage neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase inhibitor family...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#4
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/28594748/inhibition-of-spleen-tyrosine-kinase-reduces-renal-allograft-injury-in-a-rat-model-of-acute-antibody-mediated-rejection-in-sensitized-recipients
#5
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/28554738/circulating-donor-specific-anti-hla-antibodies-are%C3%A2-a%C3%A2-major-factor-in-premature-and-accelerated-allograft-fibrosis
#6
Clément Gosset, Denis Viglietti, Marion Rabant, Jérôme Vérine, Olivier Aubert, Denis Glotz, Christophe Legendre, Jean-Luc Taupin, Jean-Paul Duong Van-Huyen, Alexandre Loupy, Carmen Lefaucheur
Addressing the causes of kidney allograft-accelerated aging is an important challenge for improving long-term transplant outcomes. Here we investigated the role of circulating donor-specific anti-HLA antibodies (HLA-DSAs) in the development and the progression of kidney allograft fibrosis with inclusion of traditional risk factors for allograft fibrosis. We prospectively enrolled 1539 consecutive kidney recipients transplanted in two centers and assessed interstitial fibrosis and tubular atrophy (IF/TA) in biopsies performed at one year post-transplantation...
May 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28511172/donor-specific-anti-human-leukocyte-antigens-antibodies-acute-rejection-renal-function-and-histology-in-kidney-transplant-recipients-receiving-tacrolimus-and-everolimus
#7
Alexandra Ferreira, Claudia Felipe, Marina Cristelli, Laila Viana, Geovana Basso, Suelen Stopa, Juliana Mansur, Mayara Ivani, Adrieli Bessa, Priscila Ruppel, Wilson Aguiar, Erika Campos, Maria Gerbase-DeLima, Henrique Proença, Helio Tedesco-Silva, José Medina-Pestana
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101)...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28506366/antibody-mediated-rejection-after-liver-transplant
#8
REVIEW
Michael Lee
Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy compared with its allograft cohorts of the kidney and lung. Acute AMR is diagnosed based on specific clinical and histopathologic criteria: serum donor specific antibodies, C4d staining, histopathologic findings on liver biopsy, and exclusion of other entities. In contrast, the histologic features of chronic AMR are not as specific and it is a more challenging diagnosis to make. Treatments of acute and chronic AMR include some combination of steroids, immune-modulating agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28496948/evaluation-of-igy-antibody-as-a-polyspecific-coombs-reagent
#9
Esteban Justo Gutiérrez Calzado, Marlene Toledano Heredia, Jeorge Fernadez Duharte, Amir-Hassan Zarnani
BACKGROUND: During the last twenty years, the extraction of specific egg yolk (IgY) antibodies from the immunized chickens has been accepted as a useful alternative to the immunization of mammals. The aim of the present study was immunizing the chickens with Human Umbilical Cord Serum (HUCS) and the extraction of specific anti-human globulins (IgG, C3b, and C3d) antibodies from egg yolk in order to obtain polyspecific Coombs reagent. METHODS: The novelty of this work was the achievement of a polyclonal reagent through a very cheap alternative method in accordance with all ethical regulations required for obtaining it...
April 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28495395/study-of-the-variables-associated-with-local-complement-activation-in-iga-nephropathy
#10
Alfons Segarra-Medrano, Clara Carnicer-Caceres, Naiara Valtierra-Carmeno, Irene Agraz-Pamplona, Natalia Ramos-Terrades, Elías Jatem Escalante, Elena Ostos-Roldan
OBJECTIVES: 1. To identify the variables that are associated with urinary levels of properdin, MBL, C4d, and C5b-9 in patients with idiopathic IgA nephropathy. 2. To analyse whether urinary levels of MBL and/or C4d are useful for identifying the presence of mesangial deposits of C4d/MBL. PATIENTS AND METHOD: A total of 96 patients with IgA nephropathy were studied. Demographic, clinical and biochemical variables were recorded at the time of diagnosis. Renal lesions were quantified using the Oxford classification...
May 8, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28489305/prolonged-survival-following-pig-to-primate-liver-xenotransplantation-utilizing-exogenous-coagulation-factors-and-costimulation-blockade
#11
J A Shah, M S Patel, N Elias, N Navarro-Alvarez, I Rosales, R A Wilkinson, N J Louras, M Hertl, J A Fishman, R B Colvin, A B Cosimi, J F Markmann, D H Sachs, P A Vagefi
Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28467296/immunohistopathologic-characterization-of-plasma-cell-rich-acute-rejection-in-living-related-renal-transplant-recipients
#12
Muhammed Mubarak, Khawar Abbas, Mirza Naqi Zafar, Tahir Aziz
OBJECTIVES: Our aim was to analyze the immunohistopathologic features of plasma cell-rich acute rejection in a living-related renal transplant setting. MATERIALS AND METHODS: Renal allograft biopsies of 50 cases of plasma cell-rich acute rejection were reviewed, and the main immunohistopathologic features were analyzed. The biopsies were studied using light microscopy, immunofluorescence, and immunohistochemistry and reported according to Banff classification. Biopsy findings were correlated with graft function and outcome...
May 3, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28447925/luminex-solid-phase-crossmatch-for-de-novo-donor-specific-antibodies-in-living-donor-related-transplants
#13
Sonia Mehrotra, Raj Kumar Sharma, Mahabaleshwar Mayya, Amit Gupta, Narayan Prasad, Anupma Kaul, Dharmendra Singh Bhadauria
OBJECTIVES: There are no reports of de novo donor-specific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. MATERIALS AND METHODS: We prospectively evaluated 121 complement-dependant cytotoxicity crossmatch-negative living-donor kidney transplant recipients for development of de novo donor-specific antibodies (class I and II HLA) by solid-phase crossmatch Luminex assay after transplant. RESULTS: Of 121 recipients in our study group, 26 (21...
April 27, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28444814/chronic-antibody-mediated-rejection-in-nonhuman-primate-renal-allografts-validation-of-human-histological-and-molecular-phenotypes
#14
B A Adam, R N Smith, I A Rosales, M Matsunami, B Afzali, T Oura, A B Cosimi, T Kawai, R B Colvin, M Mengel
Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28434402/implementing-the-communication-for-development-strategy-to-improve-knowledge-and-coverage-of-measles-vaccination-in-western-chinese-immunization-programs-a-before-and-after-evaluation
#15
Ming Lu, Yao-Zhu Chu, Wen-Zhou Yu, Robert Scherpbier, Yu-Qing Zhou, Xu Zhu, Qi-Ru Su, Meng-Juan Duan, Xuan Zhang, Fu-Qiang Cui, Hua-Qing Wang, Yi-Biao Zhou, Qing-Wu Jiang
BACKGROUND: Communication for Development (C4D) is a strategy promoted by the United Nations Children's Fund to foster positive and measurable changes at the individual, family, community, social, and policy levels of society. In western China, C4D activities have previously been conducted as part of province-level immunization programs. In this study, we evaluated the association of C4D with changes in parental knowledge of immunization services, measles disease, and measles vaccine, and changes in their children's measles vaccine coverage...
April 24, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28433021/to-kink-or-not-a-search-for-long-chain-cumulenones-using-microwave-spectral-taxonomy
#16
Michael C McCarthy, Luyao Zou, Marie-Aline Martin-Drumel
A systematic search for carbon-chain cumulenones beyond H2C4O has been undertaken using microwave spectral taxonomy in combination with a pulsed jet discharge source. No evidence was found for the C2υ isomer of H2C5O or its longer derivatives, but HC(O)C4H, the longer variant of propynal, HC(O)CCH, was identified instead. Its rotational and leading centrifugal distortion constants have been derived to high accuracy from detection of both a- and b-type lines; those below 40 GHz were measured using a Fabry-Perot cavity, while lines between 40 and 72 GHz were recorded by double resonance techniques...
April 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28415773/effects-of-cd20-b-cell-infiltration-into-allografts-on-kidney-transplantation-outcomes-a-systematic-review-and-meta-analysis
#17
REVIEW
Yingying Lu, Bingjue Li, Qixia Shen, Rending Wang, Zhimin Chen, Hong Jiang, Jianghua Chen
The effects of CD20+ B-cell infiltration during acute rejection on graft outcomes are controversial. The objective of this systematic review and meta-analysis was to clarify this issue. We performed a systematic literature search for studies published up to January 14, 2016. A total of 5 studies, with 200 patients, were included. The presence of CD20+ B cells in renal biopsies during allograft rejection was associated with graft loss and steroid resistance. No association of CD20+ B-cell infiltration with C4d-positive staining of the peritubular capillaries in renal biopsies was found in the analysis of patients who experienced kidney graft rejection...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389175/validation-of-a-multi-analyte-panel-with-cell-bound-complement-activation-products-for-systemic-lupus-erythematosus
#18
Thierry Dervieux, John Conklin, Jo-Anne Ligayon, Leilani Wolover, Tyler O'Malley, Roberta Vezza Alexander, Arthur Weinstein, Claudia A Ibarra
BACKGROUND: We describe the analytical validation of an assay panel intended to assist clinicians with the diagnosis of systemic lupus erythematosus (SLE). The multi-analyte panel includes quantitative assessment of complement activation and measurement of autoantibodies. METHODS: The levels of the complement split product C4d bound to erythrocytes (EC4d) and B-lymphocytes (BC4d) (expressed as mean fluorescence intensity [MFI]) are measured by quantitative flow cytometry, while autoantibodies (inclusive of antinuclear and anti-double stranded DNA antibodies) are determined by immunoassays...
April 5, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28357484/new-approach-for-cystic-fibrosis-diagnosis-based-on-chloride-potassium-ratio-analyzed-in-non-invasively-obtained-skin-wipe-sweat-samples-by-capillary-electrophoresis-with-contactless-conductometric-detection
#19
Pavol Ďurč, František Foret, Eva Pokojová, Lukáš Homola, Jana Skřičková, Vladimír Herout, Milan Dastych, Hana Vinohradská, Petr Kubáň
A new approach for sweat analysis used in cystic fibrosis (CF) diagnosis is proposed. It consists of a noninvasive skin-wipe sampling followed by analysis of target ions using capillary electrophoresis with contactless conductometric detection (C4D). The skin-wipe sampling consists of wiping a defined skin area with precleaned cotton swab moistened with 100 μL deionized water. The skin-wipe sample is then extracted for 3 min into 400 μL deionized water, and the extract is analyzed directly. The developed sampling method is cheap, simple, fast, and painless, and can replace the conventional pilocarpine-induced sweat chloride test commonly applied in CF diagnosis...
March 29, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28341889/complement-regulation-and-kidney-diseases-recent-knowledge-of-the-double-edged-roles-of-complement-activation-in-nephrology
#20
REVIEW
Masashi Mizuno, Yasuhiro Suzuki, Yasuhiko Ito
The complement activation system plays important roles to maintain homeostasis in the host and to fight foreign invaders to protect the host. Therefore, the complement system is considered a core part of innate immunity which also cross-talks to acquired immunity. In the history of nephrology, the complement system is familiar to us, because complement protein or fragment deposition, including C3, C4, C1q, and/or C4d, is routinely estimated by immunohistochemistry to diagnose renal pathologies. The relationships between pathological mechanisms and complement activation have been investigated for renal diseases such as post-infectious glomerulonephritis, lupus nephritis, and primary membranoproliferative glomerulonephritis, which are usually accompanied by hypocomplementemia...
March 24, 2017: Clinical and Experimental Nephrology
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