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C1q HLA antibodies

Sylvie Ferrari-Lacraz
The diagnosis of acute antibody mediated rejection (ABMR) after kidney transplantation is based on three parameters: 1) decreased renal function, 2) histopathological signs of rejection, 3) presence of Donor Specific Antibody (DSA) [1]. Patient survival, as well as graft survival have improved since 5 to 10 years [2], thanks to several factors, including better management of patients, better immunosuppressive regimens, detection and avoidance of DSA. Although anti-HLA antibodies follow-up have improved ABMR management, its treatment remains challenging, and outcome may be worsened because of a delay in the diagnosis...
February 6, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
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
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 11, 2017: Transplant Immunology
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
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
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
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...
November 30, 2016: Néphrologie & Thérapeutique
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...
November 18, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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)...
October 7, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
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
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
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...
August 8, 2016: American Journal of Transplantation
Denis Viglietti, Alexandre Loupy, Dewi Vernerey, Carol Bentlejewski, Clément Gosset, Olivier Aubert, Jean-Paul Duong van Huyen, Xavier Jouven, Christophe Legendre, Denis Glotz, Adriana Zeevi, Carmen Lefaucheur
The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor-specific anti-HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post-transplant clinical events...
February 2017: Journal of the American Society of Nephrology: JASN
Erika M Cook, Margaret A Lindorfer, Hilma van der Horst, Simone Oostindie, Frank J Beurskens, Janine Schuurman, Clive S Zent, Richard Burack, Paul W H I Parren, Ronald P Taylor
Recently, we demonstrated that IgG Abs can organize into ordered hexamers after binding their cognate Ags expressed on cell surfaces. This process is dependent on Fc:Fc interactions, which promote C1q binding, the first step in classical pathway complement activation. We went on to engineer point mutations that stimulated IgG hexamer formation and complement-dependent cytotoxicity (CDC). The hexamer formation-enhanced (HexaBody) CD20 and CD38 mAbs support faster, more robust CDC than their wild-type counterparts...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jonathan Visentin, Albane Chartier, Layal Massara, Gabriel Linares, Gwendaline Guidicelli, Elodie Blanchard, Marie Parrens, Hugues Begueret, Claire Dromer, Jean-Luc Taupin
BACKGROUND: The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on graft survival is recognized in lung transplantation, but not all serum DSAs appear to be harmful. We wondered whether in situ DSA detection from graft biopsy specimens could help in identifying lung transplant recipients (LTRs) at higher risk for graft loss. METHODS: Class I and II HLA antibody single-antigen flow bead assays were performed in 53 LTRs to identify immunoglobulin G DSA in biopsy specimen eluates and in sera and to evaluate C1q binding ability of DSA in sera...
December 2016: Journal of Heart and Lung Transplantation
Craig J Taylor, Vasilis Kosmoliaptsis, Jessie Martin, Graham Knighton, Dermot Mallon, J Andrew Bradley, Sarah Peacock
BACKGROUND: Solid-phase assays to distinguish complement binding from noncomplement binding HLA-specific antibodies have been introduced, but technical limitations may compromise their interpretation. We have examined the extent to which C1q-binding to HLA-class I single-antigen beads (SAB) is influenced by denatured HLA on SAB, antibody titre, and complement interference that causes a misleading low assessment of HLA-specific antibody levels. METHODS: Sera from 25 highly sensitized patients were tested using Luminex IgG-SAB and C1q-SAB assays...
June 14, 2016: Transplantation
Anat R Tambur, Denis Glotz, Nancy D Herrera, Erik N Chatroop, Tal Roitberg, John J Friedewald, David Gjertson
Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment...
August 2016: Human Immunology
D Thammanichanond, P Wiwattanathum, T Mongkolsuk, S Kantachuvesiri, S Worawichawong, S A Vallipakorn, P Kitpoka
BACKGROUND: Kidney transplant recipients who have pretransplant donor-specific human leukocyte antigen (HLA) antibodies have greater risk for developing allograft rejection and allograft loss. However, there is a varied effect of graft injury among patients with pretransplantation donor-specific antibodies (DSA). The difference of complement activating ability may be the reason why some DSA are detrimental to kidney allograft. This study aimed to investigate the association between pretransplantation C1q-binding DSA and clinical outcomes...
April 2016: Transplantation Proceedings
Ali H Hajeer
Detection of donor-specific anti-HLA antibodies in patients with kidney graft, or awaiting kidney graft, acts as a predictor for antibody mediated rejection. Several methods are in practice for the detection of anti-HLA antibodies; including the latest introduction of C1q-binding anti-HLA antibody method. This method depends on detecting complement fixing anti-HLA antibodies on single antigen beads using C1q as the marker for the presence of those antibodies. Here we discuss recent data on this method and present a working hypothesis for explaining the inability of this method to detect low titer anti-HLA antibodies...
May 2016: Saudi Journal of Kidney Diseases and Transplantation
Carrie A Schinstock, Manish J Gandhi, Mark D Stegall
The development of sensitive methods for alloantibody detection has been a significant advance in clinical transplantation. However, the complexity of the data from solid phase and crossmatch assays has led to potential confusion about how to use the results for clinical decision making. The goal of this review is to provide a practical guide for transplant physicians for the interpretation of antibody data to supplement consultation with local tissue typing experts. Sources of variability in both the solid phase and crossmatch assay are discussed as are recent data regarding C1q binding antibodies and IgG subclass testing...
August 2016: Transplantation
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