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Complement kidney donor

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https://www.readbyqxmd.com/read/29757900/detection-of-complement-binding-donor-specific-antibodies-not-igg-antibody-strength-nor-c4d-status-at-antibody-mediated-rejection-diagnosis-is-an-independent-predictor-of-kidney-graft-failure
#1
Jorge Malheiro, Sofia Santos, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Manuela Almeida, Sofia Pedroso, Idalina Beirão, António Castro-Henriques, António Cabrita
BACKGROUND: Antibody-mediated rejection (ABMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available. METHODS: We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with ABMR C4d status, both indirect signs of complement activation, improve risk stratification at time of ABMR. Hence, among 467 patients in whom ≥1 graft biopsy was performed between 2008 and 2015, we included 56 with ABMR according to Banff'15 criteria...
May 3, 2018: Transplantation
https://www.readbyqxmd.com/read/29661469/successful-7-year-eculizumab-treatment-of-plasmapheresis-resistant-recurrent-atypical-hemolytic-uremic-syndrome-due-to-complement-factor-h-hybrid-gene-a-case-report
#2
K Vondrák, T Seeman
Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to 70% of the patients have a genetic mutation in the encoding components of complement activation or anti-complement factor H autoantibodies. The risk of recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal antibody that binds complement protein C5, has shown to be highly effective in patients with aHUS; however, there are only few reports on the efficacy and safety of long-term eculizumab treatment in children with recurrent aHUS...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29659162/clinical-utility-of-complement-dependent-c3d-assay-in-kidney-recipients-presenting-with-late-allograft-dysfunction
#3
James H Lan, David Gjertson, Ying Zheng, Stephanie Clark, Elaine F Reed, J Michael Cecka
The objective of this study was to evaluate the utility of a complement-dependent C3d assay to risk-stratify donor-specific antibodies (DSA) in a multicenter cohort of kidney recipients presenting with new-onset clinical dysfunction. One hundred and six subjects with evidence of DSA at a mean period of 5.3 ± 5.0 years posttransplant underwent testing using C3d reagents. C3d positivity was strongly associated with both the peak and sum IgG DSA MFI, with 98.3% (n=57/58) of strongly reactive sera (peak MFI >10,000) eliciting a positive signal...
April 16, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29596992/complement-fixing-donor-specific-anti-hla-antibodies-and-kidney-allograft-failure
#4
Helena B Cazarote, Silvia Shimakura, Joana S Valdameri, Fabiana L C Contieri, Cristina Q C von Glehn, Carlos M Aita, Michelle F Susin, Vanessa Santos Sotomaior, Renata Glehn-Ponsirenas
Detection of donor-specific antibodies (DSA) has improved the risk classification and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA C1q-binding ability has been shown to improve the individual risk classification of transplant patients for allograft loss, especially when detected after transplantation. The aim of this study was to evaluate the additional clinical impact of C1q-binding DSA detection in a population that was extensively monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were followed-up at multiple time points for up to 5 years after transplantation for the presence of anti-HLA DSA-IgG total...
March 26, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29579857/cytomegalovirus-infection-monitoring-based-on-interferon-gamma-release-assay-in-kidney-transplantation
#5
M D C De Gracia-Guindo, M D C Ruiz-Fuentes, P Galindo-Sacristán, J M Osorio-Moratalla, N Ruiz-Fuentes, J Rodriguez Granger, A Osuna-Ortega
BACKGROUND: Cytomegalovirus (CMV) is the most common viral infection after kidney transplantation and is associated with significant morbidity and mortality. Recent studies showed that CMV-specific CD8+ T cells play the crucial role in protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN-γ) release assay (IGRA test) that measures the IFN-γ response to a range of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility of QF-CMV assay to predict CMV infection in kidney transplant recipients and evaluated if reactive result in QF-CMV test could be predictor of the duration of treatment...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29561066/safety-immunogenicity-pharmacokinetics-and-efficacy-of-degradation-of-anti-hla-antibodies-by-ides-imlifidase-in-chronic-kidney-disease-patients
#6
Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics and efficacy of the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS, Imlifidase) was assessed in a single centre, open label ascending dose study in highly sensitised chronic kidney disease patients. Eight patients with cytotoxic panel-reactive antibodies (median cytotoxic PRA of 64%) at enrolment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 (n=3); 0.25 mg/kg x1 (n=3) or 0.25 mg/kg x2 (n=2)). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
March 21, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29478054/bringing-home-the-bacon-update-on-the-state-of-kidney-xenotransplantation
#7
David K C Cooper, H Iwase, L Wang, T Yamamoto, Qi Li, J Li, H Zhou, H Hara
BACKGROUND: There is a continuing critical shortage of organs from deceased human donors for transplantation, particularly for patients awaiting kidney transplantation. Efforts are being made to resolve the donor kidney shortage by the transplantation of kidneys from genetically-engineered pigs. SUMMARY: This review outlines the pathobiological barriers to pig organ xenotransplantation in primates, which include (i) antibody-dependent complement-mediated rejection, (ii) a T cell-mediated elicited antibody and cellular response, (iii) coagulation dysregulation between pigs and primates, and (iv) a persistent inflammatory response...
2018: Blood Purification
https://www.readbyqxmd.com/read/29475090/elevated-intragraft-expression-of-innate-immunity-and-cell-death-related-markers-is-a-risk-factor-for-adverse-graft-outcome
#8
Jianxin Yang, Malou L H Snijders, Geert W Haasnoot, Cees van Kooten, Marko Mallat, Johan W de Fijter, Marian C Clahsen-van Groningen, Frans H J Claas, Michael Eikmans
BACKGROUND: Molecules of the innate immune response are increasingly recognized as important mediators in allograft injury during and after kidney transplantation. We therefore aimed to establish the relationship between the expression of these genes at implantation, during an acute rejection (AR) and on graft outcome. METHODS: A total of 19 genes, including Toll like receptors (TLRs), complement components and regulators, and apoptosis-related genes were analyzed at the mRNA level by qPCR in 123 biopsies with acute rejection and paired pre-transplantation tissue (n = 75)...
February 20, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29464832/differential-effects-of-donor-specific-hla-antibodies-in-living-versus-deceased-donor-transplant
#9
E G Kamburova, B W Wisse, I Joosten, W A Allebes, A van der Meer, L B Hilbrands, M C Baas, E Spierings, C E Hack, F E van Reekum, A D van Zuilen, M C Verhaar, M L Bots, A C A D Drop, L Plaisier, M A J Seelen, J S F Sanders, B G Hepkema, A J A Lambeck, L B Bungener, C Roozendaal, M G J Tilanus, C E Voorter, L Wieten, E M van Duijnhoven, M Gelens, M H L Christiaans, F J van Ittersum, S A Nurmohamed, N M Lardy, W Swelsen, K A van der Pant, N C van der Weerd, I J M Ten Berge, F J Bemelman, A Hoitsma, P J M van der Boog, J W de Fijter, M G H Betjes, S Heidt, D L Roelen, F H Claas, H G Otten
The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch...
February 21, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29407333/eculizumab-for-prevention-of-antibody-mediated-rejection-in-blood-group-incompatible-renal-transplantation
#10
P West-Thielke, K Progar, M Campara, N Jasiak, L Gallon, I Tang, M Spaggiari, I Tzvetanov, E Benedetti
Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29405445/the-possible-critical-role-of-t-cell-help-in-dsa-mediated-graft-loss
#11
REVIEW
Caner Süsal, Antonij Slavcev, Lien Pham, Martin Zeier, Christian Morath
In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect...
February 6, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29370420/c3-glomerulonephritis-secondary-to-mutations-in-factors-h-and-i-rapid-recurrence-in-deceased-donor-kidney-transplant-effectively-treated-with-eculizumab
#12
Neetika Garg, Yuzhou Zhang, Anne Nicholson-Weller, Eliyahu V Khankin, Nicolò Ghiringhelli Borsa, Nicole C Meyer, Susan McDermott, Isaac E Stillman, Helmut G Rennke, Richard J Smith, Martha Pavlakis
Background: C3 glomerulonephritis (C3GN) is caused by alternate complement pathway over-activation. It frequently progresses to end-stage renal disease, recurs in two-thirds of transplants and in half of these cases progresses to allograft loss. There is currently no proven treatment for C3GN. Case Presentation: We describe a family segregating pathogenic alleles of complement factor H and I (CFH and CFI). The only member carrying both mutations developed C3GN. Prolonged delayed graft function after deceased donor transplantation, heavy proteinuria and isolated C3 hypocomplementemia prompted an allograft biopsy confirming diagnosis of recurrent C3GN...
January 23, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29359453/strong-xenoprotective-function-by-single-copy-transgenes-placed-sequentially-at-a-permissive-locus
#13
Beate Rieblinger, Konrad Fischer, Alexander Kind, Benedikt S Saller, Wiebke Baars, Marion Schuster, Lelia Wolf-van Buerck, Andrea Schäffler, Tatiana Flisikowska, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Krzysztof Flisikowski, Eckhard Wolf, Jochen Seissler, Reinhard Schwinzer, Angelika Schnieke
BACKGROUND: Multiple xenoprotective transgenes are best grouped at a single locus to avoid segregation during breeding and simplify production of donor animals. METHODS: We used transgene stacking to place a human CD55 transgene adjacent to a human heme oxygenase 1 construct at the porcine ROSA26 locus. A transgenic pig was analyzed by PCR, RT-PCR, droplet digital PCR, immunohistochemistry, immunofluorescence, and flow cytometry. Resistance to complement-mediated cell lysis and caspase 3/7 activation were determined in vitro...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29312863/human-leukocyte-antigen-typing-and-crossmatch-a-comprehensive-review
#14
REVIEW
Mohammed Mahdi Althaf, Mohsen El Kossi, Jon Kim Jin, Ajay Sharma, Ahmed Mostafa Halawa
Renal transplantation remains the best option for patients suffering from end stage renal disease (ESRD). Given the worldwide shortage of organs and growing population of patients with ESRD, those waitlisted for a transplant is ever expanding. Contemporary crossmatch methods and human leukocyte antigen (HLA) typing play a pivotal role in improving organ allocation and afford better matches to recipients. Understanding crossmatch as well as HLA typing for renal transplantation and applying it in clinical practice is the key step to achieve a successful outcome...
December 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/29288041/global-quality-assessment-of-liver-allograft-c4d-staining-during-acute-antibody-mediated-rejection-in-formalin-fixed-paraffin-embedded-tissue
#15
Desley A H Neil, Christopher O Bellamy, Maxwell Smith, Hinori Haga, Yoh Zen, Mylene Sebagh, Kristine Ruppert, John Lunz, Stefan G Hübscher, Anthony 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...
March 2018: Human Pathology
https://www.readbyqxmd.com/read/29243394/the-banff-2017-kidney-meeting-report-revised-diagnostic-criteria-for-chronic-active-t-cell-mediated-rejection-antibody-mediated-rejection-and-prospects-for-integrative-endpoints-for-next-generation-clinical-trials
#16
M Haas, A Loupy, C Lefaucheur, C Roufosse, D Glotz, D Seron, B J Nankivell, P F Halloran, R B Colvin, Enver Akalin, N Alachkar, S Bagnasco, Y Bouatou, J U Becker, L D Cornell, J P Duong van Huyen, I W Gibson, Edward S Kraus, R B 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 2 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 2 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 underimmunosuppression...
February 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29238731/porcine-to-human-heart-transplantation-is-clinical-application-now-appropriate
#17
REVIEW
Christopher G A McGregor, Guerard W Byrne
Cardiac xenotransplantation (CXTx) is a promising solution to the chronic shortage of donor hearts. Recent advancements in immune suppression have greatly improved the survival of heterotopic CXTx, now extended beyond 2 years, and life-supporting kidney XTx. Advances in donor genetic modification (B4GALNT2 and CMAH mutations) with proven Gal-deficient donors expressing human complement regulatory protein(s) have also accelerated, reducing donor pig organ antigenicity. These advances can now be combined and tested in life-supporting orthotopic preclinical studies in nonhuman primates and immunologically appropriate models confirming their efficacy and safety for a clinical CXTx program...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29229189/immunoproteasome-inhibition-prevents-chronic-antibody-mediated-allograft-rejection-in-renal-transplantation
#18
Jun Li, Michael Basler, Gerardo Alvarez, Thomas Brunner, Christopher J Kirk, Marcus Groettrup
Chronic antibody-mediated rejection is the major cause of fading allograft function and loss after renal transplantation. Currently, pharmacological agents for the suppression of chronic antibody-mediated rejection are lacking. Non-selective proteasome inhibitors suppress antibody-mediated allograft rejection. However, extensive adverse side effects of these inhibitors severely limit their application. In contrast, immunoproteasome inhibition is effective in preclinical models of autoimmune diseases and was applied over weeks without obvious adverse side effects...
March 2018: Kidney International
https://www.readbyqxmd.com/read/29212248/impact-of-complement-component-3-4-5-single-nucleotide-polymorphisms-on-renal-transplant-recipients-with-antibody-mediated-rejection
#19
Zijie Wang, Haiwei Yang, Miao Guo, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu
Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction in kidney transplantation. The complement system is considered to be associated with the generation of alloreative antibodies and donor-specific antibodies. However, the association of complement single nucleotide polymorphisms (SNPs) with ABMR still remained unclear. Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected, and analyzed by next-generation sequencing with an established gene panel...
November 7, 2017: Oncotarget
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
#20
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
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