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Donor specific antibodies

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https://www.readbyqxmd.com/read/29473178/pas-c-platelets-contain-less-plasma-protein-lower-anti-a-and-anti-b-titers-and-decreased-hla-antibody-specificities-compared-to-plasma-platelets
#1
Stuart P Weisberg, Beth H Shaz, Gizem Tumer, Chris C Silliman, Marguerite R Kelher, Claudia S Cohn
BACKGROUND: Platelets (PLTs) collected and stored in PLT additive solution Intersol (PAS-C) are presumed to reduce recipient exposure to donor plasma components; however, the effects of PAS-C on PLT supernatant composition are poorly defined. Therefore, we compared the total protein concentration, isohemagglutinin titers, and HLA antibodies in supernatants of PAS-C PLTs to plasma PLTs. STUDY DESIGN AND METHODS: Apheresis PLTs from group O blood donors were collected into either 100% donor plasma (n = 50) or a mixture of 65% PAS-C/35% donor plasma (n = 50)...
February 22, 2018: Transfusion
https://www.readbyqxmd.com/read/29470351/severe-unresolved-cholestasis-due-to-unknown-aetiology-leading-to-early-allograft-failure-within-the-first-3-months-of-liver-transplantation
#2
Roberta Angelico, Undine A Gerlach, Bridget K Gunson, Desley Neil, Hynek Mergental, John Isaac, Paolo Muiesan, Darius Mirza, M Thamara Pr Perera
BACKGROUND: Causes of severe cholestasis following liver transplantation(LT) are multi-factorial; whilst the aetiology is predictable in some, others culminate in graft/patient loss without a definitive cause identified. Severe cholestasis is usually associated with overlapped histological findings of rejection and biliary features, and diagnostic interpretation may pose a challenge. METHODS: This is 10-year retrospective analysis of patients with unexplained severe cholestasis resulting in death/graft loss within 90-days of LT...
February 20, 2018: Transplantation
https://www.readbyqxmd.com/read/29470350/analysis-of-luminex-based-algorithms-to-define-unacceptable-hla-antibodies-in-cdc-crossmatch-negative-kidney-transplant-recipients
#3
Daniel Zecher, Christian Bach, Adrian Preiss, Christoph Staudner, Kirsten Utpatel, Matthias Evert, Bettina Jung, Tobias Bergler, Carsten A Böger, Bernd M Spriewald, Bernhard Banas
BACKGROUND: HLA-specific antibodies detected by solid phase assays are increasingly used to define unacceptable HLA antigen mismatches (UAM) prior to renal transplantation. The accuracy of this approach is unclear. METHODS: Day of transplant sera from 211 CDC-crossmatch-negative patients were retrospectively analyzed for donor-specific anti-HLA antibodies (DSA) using Luminex technology. HLA were defined as UAM if DSA had mean fluorescence intensity above (I) 3000 (patients retransplanted and those with DSA against HLA class I and II) or 5000 (all other patients), (II) 5000 for HLA A, B and DR and 10,000 for HLA DQ or (III) 10,000 (all HLA)...
February 20, 2018: Transplantation
https://www.readbyqxmd.com/read/29470345/summary-of-2017-fda-public-workshop-antibody-mediated-rejection-in-kidney-transplantation
#4
Ergun Velidedeoglu, Marc W Cavaillé-Coll, Shukal Bala, Ozlem A Belen, Yan Wang, Renata Albrecht
BACKGROUND: Despite major advances in understanding the pathophysiology of antibody mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T-cell mediated rejection (TCMR), de novo donor specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. METHODS: On April 12-13, 2017, the Food and Drug Administration (FDA) sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in GFR, and challenges of clinical trial design for the prevention and treatment of AMR...
February 20, 2018: Transplantation
https://www.readbyqxmd.com/read/29465656/herpes-simplex-virus-type-2-seroprevalence-among-different-national-populations-of-middle-east-and-north-african-males
#5
Soha R Dargham, Gheyath K Nasrallah, Enas S Al-Absi, Layla I Mohammed, Rana S Al-Disi, Mariam Y Nofal, Laith J Abu-Raddad
BACKGROUND: There are limited data on herpes simplex virus type 2 (HSV-2) seroprevalence in the Middle East and North Africa (MENA). We examined country- and age-specific HSV-2 seroprevalence among select MENA populations residing in Qatar. METHODS: Sera were collected from male blood donors attending Hamad Medical Corporation June 2013-2016. Specimens were screened for anti-HSV-2 IgG antibodies following a two-test algorithm: HerpeSelect® 2 ELISA was used to identify HSV-2 positive specimens, and Euroline-WB was used to confirm positive and equivocal specimens for final HSV-2 status...
January 16, 2018: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/29464837/isolated-vascular-v-lesions-in-liver-allografts-how-to-approach-this-unusual-finding
#6
H L Stevenson, M M Prats, K Isse, A Zeevi, Y Avitzur, V L Ng, A J Demetris
According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with co-existent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified 9 patients at a mean of 1,805 days post-transplantation and compared these to matched controls...
February 21, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29464832/differential-effects-of-donor-specific-hla-antibodies-in-living-versus-deceased-donor-transplantation
#7
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 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 (DSA) is associated with increased risk of graft failure after kidney transplantation. We hypothesized that DSA against HLA class-I, -II or both indicate a different risk for graft loss between deceased- and living-donor transplantation. In this study we investigated the impact of pretransplant DSA, assessed using single antigen bead assays, on long-term graft survival in 3237 deceased- and 1487 living-donor kidney transplantations with a negative complement-dependent crossmatch...
February 21, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29457879/the-good-the-bad-and-the-ugly-of-luminex-donor-specific-cross-match
#8
M Chowdhry, R N Makroo, Y Thakur, V Sharma, M Singh, M Kumar
The presence of donor specific antibodies directed against human leukocyte antigen significantly influences renal transplant due to antibody mediated rejection (AMR). We performed the screening of pre-renal transplant patients for preformed anti HLA antibodies using Antihuman globulin augmented-CDC crossmatch (AHG-CDCXm), Luminex donor specific crossmatch (LumXm) and HLA antibody screening. Seven hundred and fifty four patients were assessed for LumXm. HLA antibody screening was possible in 325 out of 754 cases...
February 19, 2018: HLA
https://www.readbyqxmd.com/read/29452978/the-management-of-antibodies-in-heart-transplantation-an-ishlt-consensus-document
#9
Jon Kobashigawa, Monica Colvin, Luciano Potena, Duska Dragun, Maria G Crespo-Leiro, Juan F Delgado, Michael Olymbios, Jayan Parameshwar, Jignesh Patel, Elaine Reed, Nancy Reinsmoen, E Rene Rodriguez, Heather Ross, Randall C Starling, Dolly Tyan, Simon Urschel, Andreas Zuckermann
Despite the successes from refined peri-operative management techniques and immunosuppressive therapies, antibodies remain a serious cause of morbidity and mortality for patients both before and after heart transplantation. Patients awaiting transplant who possess antibodies against human leukocyte antigen are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory support devices...
January 31, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29451342/deleterious-effect-of-anti-angiotensin-ii-type-1-receptor-antibodies-detected-pretransplant-on-kidney-graft-outcomes-is-both-proper-and-synergistic-with-donor-specific-anti-hla-antibodies
#10
Jorge Malheiro, Sandra Tafulo, Leonídio Dias, La Salete Martins, Isabel Fonseca, Idalina Beirão, António Castro-Henriques, António Cabrita
AIM: Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs with or without concomitant DSA on KT outcomes. METHODS: Seventy-six patients transplanted in 2009 were studied. DSA (MFI>1000) and/or AT1R-abs (>10UI) were detected by solid-phase assays in pre-KT sera. Multivariable Cox regression models were used to determine independent predictors of outcomes: acute rejection (AR) and graft failure...
February 16, 2018: Nephrology
https://www.readbyqxmd.com/read/29449777/a-homogeneous-time-resolved-fluorescence-immunoassay-method-for-the-measurement-of-compound-w
#11
Biao Huang, Huixin Yu, Jiandong Bao, Manda Zhang, William L Green, Sing-Yung Wu
Objective: Using compound W (a 3,3'-diiodothyronine sulfate [T 2 S] immuno-crossreactive material)-specific polyclonal antibodies and homogeneous time-resolved fluorescence immunoassay assay techniques (AlphaLISA) to establish an indirect competitive compound W (ICW) quantitative detection method. Method: Photosensitive particles (donor beads) coated with compound W or T 2 S and rabbit anti-W antibody were incubated with biotinylated goat anti-rabbit antibody. This constitutes a detection system with streptavidin-coated acceptor particle...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/29446493/anti-donor-antibody-induction-following-intramuscular-injections-of-allogeneic-mesenchymal-stromal-cells
#12
Senthilkumar Alagesan, Clara Sanz-Nogués, Xizhe Chen, Michael Creane, Thomas Ritter, Rhodri Ceredig, Timothy O'Brien, Matthew D Griffin
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice two weeks after single or repeated IM injections of fully-MHC-mismatched allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline...
February 15, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29446208/study-rationale-design-and-pre-transplant-alloantibody-status-a-first-report-of-clinical-trials-in-organ-transplantation-in-children-04-ctotc-04-in-pediatric-heart-transplantation
#13
Warren A Zuckerman, Adriana Zeevi, Kristen L Mason, Brian Feingold, Carol Bentlejewski, Linda J Addonizio, Elizabeth D Blume, Charles E Canter, Anne I Dipchand, Daphne T Hsu, Robert E Shaddy, William T Mahle, Anthony J Demetris, David M Briscoe, Thalachallour Mohanakumar, Joseph M Ahearn, David N Iklé, Brian D Armstrong, Yvonne Morrison, Helena Diop, Jonah Odim, Steven A Webber
Anti-HLA donor-specific antibodies are associated with worse outcomes following organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase post-transplant morbidity and mortality. We address this clinical challenge in a prospective, multi-center, observational cohort study of children listed for heart transplantation (CTOTC-04). Outcomes were compared among sensitized recipients who underwent transplant with positive crossmatch, non-sensitized recipients, and sensitized recipients without positive crossmatch...
February 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29445364/non-specific-effect-of-vaccines-immediate-protection-against-respiratory-syncytial-virus-infection-by-a-live-attenuated-influenza-vaccine
#14
Young J Lee, Jeong Y Lee, Yo H Jang, Sang-Uk Seo, Jun Chang, Baik L Seong
The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29444836/evaluation-of-the-elecsys%C3%A2-chagas-assay-for-the-detection-of-trypanosoma-cruzi-specific-antibodies-in-a-multicenter-study-in-europe-and-latin-america
#15
Maria Delmans Flores-Chavez, Vittorio Sambri, Volkmar Schottstedt, Fernando Aparicio Higuera-Escalante, Dieter Roessler, Monica Chaves, Tina Laengin, Alfredo Martinez, Bernhard Fleischer
Serology is the preferred method to confirm Chagas disease diagnosis and to screen blood donors. A battery of assays is often required due to the limited accuracy of single assays. The Elecsys® Chagas assay is a newly developed, double-antigen sandwich assay for use on the Elecsys® and cobas® e immunoassay analyzers, intended to identify individuals infected with Trypanosoma cruzi, for diagnosis and screening. The performance of the Elecsys® Chagas assay was evaluated in comparison with other widely used T...
February 14, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29444290/impact-of-renal-allograft-nephrectomy-on-graft-and-patient-survival-following-retransplantation-a-systematic-review-and-meta-analysis
#16
Jinwen Lin, Rending Wang, Ying Xu, Jianghua Chen
Background: It is not clear whether renal allograft removal affects the outcome of renal retransplantation. This study aimed to determine the effect of allograft nephrectomy (AN) and no-AN (No AN) on renal retransplantation. Methods: A systematic review and meta-analysis were conducted using MEDLINE, Embase and the Cochrane Library. Observational studies or randomized controlled trials including renal retransplantation recipients with AN or No-AN were included. The primary outcomes were graft survival, patient survival, acute rejection (AR) and delayed graft dysfunction; the secondary outcomes were positive panel reactive antibody rate and serum creatinine level at 1 year after retransplantation, cold ischemia time and time of hemodialysis before recent transplantation...
February 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29444269/association-of-angiotensin-ii-type-1-receptor-antibodies-with-graft-histology-function-and-survival-in-paediatric-renal-transplant-recipients
#17
Alexander Fichtner, Caner Süsal, Claudia Schröder, Britta Höcker, Susanne Rieger, Rüdiger Waldherr, Jens H Westhoff, Anja Sander, Duska Dragun, Burkhard Tönshoff
Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology...
February 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29443827/a-comparison-of-hla-molecular-mismatch-methods-to-determine-hla-immunogenicity
#18
C Wiebe, V Kosmoliaptsis, D Pochinco, C Taylor, P Nickerson
BACKGROUND: Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level, however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression. METHODS: HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development...
February 13, 2018: Transplantation
https://www.readbyqxmd.com/read/29442424/incidence-characterization-and-impact-of-newly-detected-donor-specific-anti-hla-antibody-in-the-first-year-after-pediatric-heart-transplantation-a-report-from-the-ctotc-04-study
#19
A I Dipchand, S Webber, K Mason, B Feingold, C Bentlejewski, W T Mahle, R Shaddy, C Canter, E D Blume, J Lamour, W Zuckerman, H Diop, Y Morrison, B Armstrong, D Ikle, J Odim, A Zeevi
Data on the clinical importance of newly detected donor specific antibodies (ndDSA) following pediatric heart transplantation is lacking despite mounting evidence of the detrimental effect of de novo DSA in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSA in the first year post-transplant in order to determine their incidence, pattern and clinical impact. One third of patients developed ndDSA; when present, these were mostly detected within the first 6 weeks after transplant suggesting that memory responses may predominate over true de novo DSA production in this population...
February 14, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29434741/inhibition-of-c-x-c-motif-chemokine-10-reduces-graft-loss-mediated-by-memory-cd8-t-cells-in-a-rat-cardiac-re-transplant-model
#20
Jiacheng Xu, Teng Ma, Guorong Deng, Jiawei Zhuang, Cheng Li, Shaohu Wang, Chen Dai, Xiaobiao Zhou, Zhonggui Shan, Zhongquan Qi
The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8+ Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage...
February 2018: Experimental and Therapeutic Medicine
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