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C1q HLA antibodies

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 (DSA) against human leukocyte antigens on outcomes after kidney transplantation remains controversial. 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 beads (SAB) assays (IgG and C1q kits). Patients were divided both by DSA strength (MFI < vs. ≥15000) and C1q-binding ability...
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...
August 4, 2016: 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...
June 24, 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
Farsad Eskandary, Gregor Bond, Nicolas Kozakowski, Heinz Regele, Lena Marinova, Markus Wahrmann, Željko Kikić, Helmuth Haslacher, Susanne Rasoul-Rockenschaub, Christopher C Kaltenecker, Franz König, Luis G Hidalgo, Rainer Oberbauer, Philip F Halloran, Georg A Böhmig
BACKGROUND: Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR. METHODS: Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation...
April 26, 2016: Transplantation
Rachael P Jackman, Jar-How Lee, Rui Pei, Douglas Bolgiano, Mila Lebedeva, Sherrill J Slichter, Philip J Norris
BACKGROUND: In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of 530 subjects became clinically refractory (CR) to platelets (PLTs) without lymphocytotoxicity assay (LCA)-detectable anti-HLA antibodies. The LCA only detects complement-binding antibodies and is less sensitive than newer assays. Utilizing a more sensitive bead-based assay that does not distinguish between complement-binding versus non-complement-binding antibodies, we have previously shown that while many LCA-negative (LCA-) patients do have anti-HLA antibodies, these low- to moderate-level antibodies do not predict refractoriness...
April 15, 2016: Transfusion
Alexander Fichtner, Caner Süsal, Britta Höcker, Susi Rieger, Rüdiger Waldherr, Jens H Westhoff, Anja Sander, Gerhard Opelz, Burkhard Tönshoff
BACKGROUND: We investigated the prognostic value of overall and complement-binding donor-specific HLA antibodies (DSA) in pediatric patients undergoing clinically indicated graft biopsies and their association with graft outcome and specific histological lesions. METHODS: Sera of 62 patients at time of indication biopsy ≥1 year posttransplant were assessed for DSA and C1q-fixing DSA by single-antigen bead (SAB) technology. RESULTS: Twenty-six patients (42 %) were DSA-positive at time of indication biopsy and nine (15 %) were C1q-positive...
July 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
S M Schaefer, C Süsal, G Opelz, B Döhler, L E Becker, K Klein, S Sickmüller, R Waldherr, S Macher-Goeppinger, P Schemmer, J Beimler, M Zeier, C Morath
Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL...
February 2016: HLA
P Comoli, M Cioni, A Tagliamacco, G Quartuccio, A Innocente, I Fontana, A Trivelli, A Magnasco, A Nocco, C Klersy, L Rubert, M Ramondetta, M Zecca, G Garibotto, G M Ghiggeri, M Cardillo, A Nocera, F Ginevri
Alloantibody-mediated graft injury is a major cause of kidney dysfunction and loss. The complement-binding ability of de novo donor-specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement-fixing dnDSAs and their role in antibody-mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity...
July 2016: American Journal of Transplantation
Takayuki Yamamoto, Yoshihiko Watarai, Asami Takeda, Makoto Tsujita, Takahisa Hiramitsu, Norihiko Goto, Shunji Narumi, Akio Katayama, Kunio Morozumi, Kazuharu Uchida, Takaaki Kobayashi
BACKGROUND: It is unclear whether all donor-specific antibodies (DSA) can cause chronic antibody-mediated rejection (AMR). Subclinical stage before manifestation of renal dysfunction may be a critical period for reversing AMR. The aim of our study was to identify factors related to the development of subclinical AMR and to clarify the characteristics of de novo DSA. METHODS: Eight hundred ninety-nine renal transplants were screened for HLA antibody. De novo DSA were detected in 95 patients...
October 2016: Transplantation
Junchao Cai, Paul I Terasaki, Dong Zhu, Nils Lachmann, Constanze Schönemann, Matthew J Everly, Xin Qing
BACKGROUND: We have found antibodies against denatured HLA class I antigens in the serum of allograft recipients which were not significantly associated with graft failure. It is unknown whether transplant recipients also have denatured HLA class II and MICA antibodies. The effects of denatured HLA class I, class II, and MICA antibodies on long-term graft outcome were further investigated based on their ability to fix complement c1q. MATERIALS AND METHODS: In this 4-year retrospective cohort study, post-transplant sera from 975 kidney transplant recipients were tested for antibodies against denatured HLA/MICA antigens and these antibodies were further classified based on their ability to fix c1q...
February 2016: Experimental and Molecular Pathology
Sumeyye Calp-Inal, Maria Ajaimy, Michal L Melamed, Christina Savchik, Peter Masiakos, Adriana Colovai, Enver Akalin
We aimed to determine the prevalence and clinical significance of complement-binding donor-specific antibodies (DSA) detected up to 30 years after kidney transplantation. Group 1 patients included 284 consecutive DSA negative patients who underwent kidney transplantation after 1 May 2009. Group 2 included 405 patients transplanted before this date and followed at our center with functioning allografts. DSA were tested using Luminex Single Antigen and the C1q assay. In Group 1 patients, who were monitored prospectively, 31 (11%) developed de novo DSA during a median follow-up of 2...
January 2016: Kidney International
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