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C1q HLA antibodies

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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
#1
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/28707765/tissue-microarray-methodology-identifies-complement-pathway-activation-and-dysregulation-in-progressive-multiple-sclerosis
#2
Sam Loveless, James W Neal, Owain W Howell, Katharine E Harding, Patrick Sarkies, Rhian Evans, Ryan J Bevan, Svetlana Hakobyan, Claire L Harris, Neil P Robertson, B Paul Morgan
BACKGROUND: The complement pathway has potential contributions to both white (WM) and grey matter (GM) pathology in Multiple Sclerosis (MS). A quantitative assessment of complement involvement is lacking. OBJECTIVE: Tissue MicroArray methodology was used in conjunction with immunohistochemistry to investigate the localization of complement pathway proteins in progressive MS cortical GM and subcortical WM. METHODS: Antibodies targeting complement proteins C1q, C3b, regulatory proteins C1 inhibitor (C1INH), complement receptor 1 (CR1), clusterin, factor H (FH) and the C5a anaphylatoxin receptor (C5aR) were utilised alongside standard markers of tissue pathology...
July 14, 2017: Brain Pathology
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
#3
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/28585289/effects-of-weak-non-complement-binding-hla-antibodies-on-c1q-binding
#4
G Hönger, P Amico, M-L Arnold, B M Spriewald, S Schaub
It is unknown under what conditions and to what extent weak/non-complement (C)-binding IgG subclasses (IgG2/IgG4) can block C1q-binding triggered by C-binding IgG subclasses (IgG1/IgG3). Therefore, we investigated in vitro C1q-binding induced by IgG subclass mixtures targeting the same HLA epitope. Various mixtures of HLA class II specific monoclonal antibodies of different IgG subclasses but identical V-region were incubated with HLA DRB1*07:01 beads and monitored for C1q-binding. The lowest concentration to achieve maximum C1q-binding was measured for IgG3, followed by IgG1, while IgG2 and IgG4 did not show appreciable C1q-binding...
June 5, 2017: HLA
https://www.readbyqxmd.com/read/28367453/de-novo-donor-specific-hla-antibodies-developing-early-or-late-after-transplant-are-associated-with-the-same-risk-of-graft-damage-and-loss-in-nonsensitized-kidney-recipients
#5
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago, Antonella Gurrado, Ilaria Guido, Francesca Compagno, Giacomo Garibotto, Catherine Klersy, Enrico Verrina, Gian Marco Ghiggeri, Massimo Cardillo, Patrizia Comoli, Fabrizio Ginevri
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28340811/tac-mmf-versus-csa-mmf-csa-aza-based-regimens-in-development-of-de-novo-complement-binding-anti-hla-antibodies-after-kidney-transplantation
#6
T Sahutoglu, S U Akgul, Y Caliskan, H Yazici, E Demir, E Kara, S Temurhan, F O Savran, A Turkmen
BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28284929/anti-hla-dq-antibodies-are-highly-and-independently-related-to-the-c1q-binding-capacity-of-hla-antibodies
#7
José M Arreola-Guerra, Luis E Morales-Buenrostro, Julio Granados, Natalia Castelán, Adrián de Santiago, Adriana Arvizu, Norma Gonzalez-Tableros, Mayra López, Mario Vilatobá, Josefina Alberú
The complement-binding capacity of anti-HLA antibodies (HLAabs) is recognized as a key pathogenic factor. The aim of this study is to describe the patient characteristics associated to the presence of C1q+ as well as those of the Abs per se when associated to C1q binding. METHODOLOGY: This is a cross-sectional, observational, descriptive study of patients with previous sensitizing factors and awaiting a kidney transplant (KT). We determined anti-HLA antibodies and their C1q binding capacity with the C1q assay...
March 8, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28256086/males-without-apparent-alloimmunization-could-have-hla-antibodies-that-recognize-target-hla-specificities-expressed-on-cells
#8
J Nakamura, F Nakajima, H Kamada, K Tadokoro, T Nagai, M Satake
BACKGROUND AND OBJECTIVES: Human leukocyte antigen (HLA) antibodies, which are involved in the development of transfusion-related side effects such as transfusion-related lung injury, are sometimes found in males without a history of alloimmunization (eg, transplantation and transfusion). Whether HLA antibodies in male donors can interact with their target HLA specificities expressed on cells have not been completely investigated. MATERIALS AND METHODS: The HLA antibodies detected in 7 male donors were characterized...
May 2017: HLA
https://www.readbyqxmd.com/read/28166393/donor-specific-antibodies-c1q-binding-improvement-in-kidney-graft-management
#9
COMMENT
Sylvie Ferrari-Lacraz
No abstract text is available yet for this article.
April 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28158255/improvement-in-the-definition-of-anti-hla-antibody-profile-in-highly-sensitized-patients
#10
Juan Irure, Esther Asensio, Emilio Rodrigo, Íñigo Romón, Javier Gómez, Manuel Arias, Marcos López-Hoyos, David San Segundo
The definition of anti-HLA antibody profile in highly sensitized patients on a waiting list is crucial when virtual crossmatch is used in organ allocation systems, but also when used to identify the true deleterious anti-HLA antibodies. Here we propose different levels of risk based on the results of anti-HLA antibody testing in neat serum (N) and after sera dilution (DIL) and C1q test in 18 highly sensitized patients. This group was heterogeneous in terms of anti-HLA antibody titers and their ability to fix complement...
2017: PloS One
https://www.readbyqxmd.com/read/28088367/assignment-of-c1q-binding-hla-antibodies-as-unacceptable-hla-antigens-avoids-positive-cdc-crossmatches-prior-to-transplantation-of-deceased-donor-organs
#11
David Juhl, Matthias Marget, Michael Hallensleben, Siegfried Görg, Malte Ziemann
Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed...
January 12, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/27979771/rapid-and-strong-de-novo-donor-specific-antibody-development-in-a-lung-transplant-recipient-short-communication-case-report
#12
Andrew L Lobashevsky, Kevin M Rosner, John D May, Michael D Duncan, Chadi A Hage, Erin N Lushin, Eve E Anderson, David W Roe
A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations. Twinrix, Zostavax and MMR vaccines contain viruses grown on live human lung fibroblasts (MRC-5, typed B*07:02, 44:02, and WI-38, typed B*08:01, 58:01)...
December 12, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27932179/combined-kidney-transplantation-and-splenic-fossa-auxiliary-heterotopic-liver-transplantation-in-a-highly-sensitized-recipient-a-case-report
#13
G Zhang, Y Zhu, W Qin, L Yu, G Wu, S Ma, F Wang, R Qin, X Yang, K Tao, S Yue, G Zhao, Z Yang, J Yuan, K Dou, J Yuan
BACKGROUND: Combined kidney and auxiliary orthotopic liver transplantation from the same donor is used to treat highly sensitized renal transplant recipients. Auxiliary liver can protect the transplanted kidney against hyperacute rejection. METHODS: In the current case, combined kidney and splenic fossa auxiliary heterotopic liver transplantation was performed from the same donor for a highly sensitized recipient without preoperative preconditioning. No postoperative hyperacute rejection occurred...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932124/de-novo-donor-specific-anti-human-leukocyte-antigen-antibody-detection-in-long-term-adult-liver-transplantation
#14
D San Segundo, C Alonso, P Ruiz, I Roman, M T Arias-Loste, A Cuadrado, A Puente, F Casafont, M López-Hoyos, J Crespo, E Fábrega
INTRODUCTION: Information about the consequences of de novo donor-specific anti-human leukocyte antigen (DSA) antibody development in the long term after adult liver transplantation (LT) is scarce. We conducted a cross-sectional study in LT patients with a follow-up of at least 6 years. METHODS: A total of 28 adult LT patients were included, with a median follow-up of 77 months (range, 63 to 96) and without preformed anti- human leukocyte antigen (HLA) antibodies prior to LT...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27914916/-cytotoxicity-of-natural-anti-hla-antibodies-in-moroccan-patients-awaiting-for-kidney-transplantation
#15
Nadia Benseffaj, Sanae Ouadghiri, Asmaa Drissi Bourhanbour, Asmae Noor Zerrouki, Malika Essakalli
The presence of anti-HLA antibodies in the serum of a patient result from an immune response produced during an immunizing event as transfusion, pregnancy or graft. These antibodies can be cytotoxic by activating the complement pathway via C1q and may cause organ rejection during the transplant. Some male patients awaiting kidney transplantation are seropositive for anti-HLA antibodies when they have no immunizing antecedent event. These antibodies are qualified as natural antibodies. Our work is to assess the cytotoxicity of natural anti-HLA antibodies in patients followed at the immunology laboratory of the blood transfusion service and hemovigilance (STSH) as part of the kidney transplant...
November 30, 2016: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/27862352/de-novo-donor-specific-anti-hla-antibodies-after-kidney-transplantation-are-associated-with-impaired-graft-outcome-independently-of-their-c1q-binding-ability
#16
Teresa Kauke, Cornelia Oberhauser, Viviane Lin, Michaela Coenen, Michael Fischereder, Andrea Dick, Ulf Schoenermarck, Markus Guba, Joachim Andrassy, Jens Werner, Bruno Meiser, Martin Angele, Manfred Stangl, Antje Habicht
Many aspects of post-transplant monitoring of donor-specific (DSA) and non-donor-specific (nDSA) anti-HLA antibodies on renal allograft survival are still unclear. Differentiating them by their ability to bind C1q may offer a better risk assessment. We retrospectively investigated the clinical relevance of de novo C1q-binding anti-HLA antibodies on graft outcome in 611 renal transplant recipients. Acute rejection (AR), renal function, and graft survival were assessed within a mean follow-up of 6.66 years. Post-transplant 6...
April 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27717025/determining-donor-specific-antibody-c1q-binding-ability-improves-the-prediction-of-antibody-mediated-rejection-in-human-leucocyte-antigen-incompatible-kidney-transplantation
#17
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
Detrimental impact of preformed donor-specific antibodies (DSAs) against human leucocyte antigens on outcomes after kidney transplantation are well documented, however, the value of their capacity to bind complement for predicting antibody-mediated rejection (AMR) and graft survival still needs to be confirmed. We aimed to study DSA characteristics (strength and C1q binding) that might distinguish harmful DSA from clinically irrelevant ones. We retrospectively studied 60 kidney-transplanted patients with preformed DSA detected by single antigen bead (SAB) assays (IgG and C1q kits), from a cohort of 517 kidney graft recipients (124 with detectable anti-HLA antibodies)...
April 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27569975/prediction-of-complement-binding-capacity-of-hla-antibodies-based-on-mean-fluorescence-intensity
#18
J Zhao, Y X Fu, T Yang, Z Y Shen, C L Wu
BACKGROUND: Human leukocyte antigen (HLA) antibodies estimated by Luminex single-antigen beads, especially those that fix complement, are associated with antibody-mediated rejection and graft failure. However, the relationship between HLA antibody strength and complement-binding ability is controversial. METHODS: Serum samples of 31 sensitized renal patients waiting for renal transplantation were retrospectively analyzed by IgG-Luminex to identify HLA antibodies and in parallel by C1q-Luminex to determine the complement binding of HLA antibodies...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27569927/association-of-c1q-binding-status-with-de-novo-hla-antibody-clinical-features-and-allograft-function-in-kidney-transplantation-patients-during-eight-years-of-dynamic-follow-up
#19
X Wei, X Yuan, M Sun, Z Pan, L Hu, L Wang, J He, J Hou
BACKGROUND: C1q-binding donor-specific antibody (DSA) is detrimental to transplanted kidney function. However, the factors that affect C1q binding status are unclear. METHODS: A total of 519 samples from 129 consecutive kidney transplantation patients during 8 years of dynamic follow-up were collected for HLA antibody (Ab) screening and C1q detection. RESULTS: Among the detected HLA Abs, the majority were class II, and the DQ subtypes composed the highest proportion...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27501275/kidney-intragraft-homing-of-de-novo-donor-specific-hla-antibodies-is-an-essential-step-of-antibody-mediated-damage-but-not-per-se-predictive-of-graft-loss
#20
A Nocera, A Tagliamacco, M Cioni, A Innocente, I Fontana, G Barbano, A Carrea, M Ramondetta, A Sementa, S Basso, G Quartuccio, C Klersy, M Bertocchi, E Verrina, G Garibotto, G M Ghiggeri, M Cardillo, P Comoli, F Ginevri
Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens...
March 2017: American Journal of Transplantation
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