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donor specific antibody

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https://www.readbyqxmd.com/read/29913037/does-human-leukocyte-antigens-sensitization-matter-for-xenotransplantation
#1
REVIEW
Guerard W Byrne
The major histocompatibility complex class I and class II human leukocyte antigens (HLA) play a central role in adaptive immunity but are also the dominant polymorphic proteins targeted in allograft rejection. Sensitized patients with high levels of panel-reactive anti-HLA antibody (PRA) are at risk of early allograft injury, rejection, reduced allograft survival and often experience prolonged waiting times prior to transplantation. Xenotransplantation, using genetically modified porcine organs, offers a unique source of donor organs for these highly sensitized patients if the anti-HLA antibody, which places the allograft at risk, does not also enhance anti-pig antibody reactivity responsible for xenograft rejection...
May 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29912041/cincinnati-protocol-for-preoperative-screening-and-donor-selection-for-ocular-surface-stem-cell-transplantation
#2
Albert Y Cheung, Enrica Sarnicola, Khaliq H Kurji, Amit Govil, Gautham Mogilishetty, Medi Eslani, Elizabeth Wright, Paul Brailey, Edward J Holland
PURPOSE: To describe our process for preoperative screening and donor selection for ocular surface stem cell transplantation (OSST). METHODS: A 7-year retrospective chart review was performed on limbal stem cell deficiency patients. The inclusion criterion was all patients who underwent an OSST procedure. The exclusion criterion was eyes with unilateral disease in which an autograft was performed. Data for human leukocyte antigen (HLA) typing, virtual crossmatching, donor-specific antibody, and panel reactive antibody level were obtained...
June 14, 2018: Cornea
https://www.readbyqxmd.com/read/29908316/the-clinical-significance-of-epitope-mismatch-load-in-kidney-transplantation-a-multicentre-study
#3
Liesbeth Daniëls, Maarten Naesens, Jean-Louis Bosmans, Daniel Abramowicz, Evi Nagler, Steven Van Laecke, Patrick Peeters, Dirk Kuypers, Marie-Paule Emonds
Since the advent of kidney transplantation a key strategy for maximising graft survival by avoiding allorecognition has been to minimise HLA mismatching between donor and recipient. As HLA antibodies are now recognised as being specific for epitopes and donor-recipient HLA mismatch at the amino acid level can now be determined, HLA epitope mismatch load could be a better predictor for dnDSA development than classical HLA antigen mismatch calculation. This hypothesis has been investigated by other studies and the aim of our multicentre study was to confirm this observation in our population...
June 13, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29904381/the-calcineurin-inhibitor-tacrolimus-specifically-suppresses-human-t-follicular-helper-cells
#4
Elizabeth F Wallin, Danika L Hill, Michelle A Linterman, Kathryn J Wood
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29902635/overcoming-non-specific-binding-to-measure-the-active-concentration-and-kinetics-of-serum-anti-hla-antibodies-by-surface-plasmon-resonance
#5
Jonathan Visentin, Lionel Couzi, Claire Dromer, Martine Neau-Cransac, Gwendaline Guidicelli, Vincent Veniard, Karine Nubret-le Coniat, Pierre Merville, Carmelo Di Primo, Jean-Luc Taupin
Human leukocyte antigen (HLA) donor-specific antibodies are key serum biomarkers for assessing the outcome of transplanted patients. Measuring their active concentration, i.e. the fraction that really interacts with donor HLA, and their affinity could help deciphering their pathogenicity. Surface plasmon resonance (SPR) is recognized as the gold-standard for measuring binding kinetics but also active concentrations, without calibration curves. SPR-based biosensors often suffer from non-specific binding (NSB) occurring with the sensor chip surface and the immobilized targets, especially for complex media such as human serum...
June 7, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29898396/co-evolution-of-hiv-envelope-and-apex-targeting-neutralizing-antibody-lineage-provides-benchmarks-for-vaccine-design
#6
Kimmo Rantalainen, Zachary T Berndsen, Sasha Murrell, Liwei Cao, Oluwarotimi Omorodion, Jonathan L Torres, Mengyu Wu, Jeffrey Umotoy, Jeffrey Copps, Pascal Poignard, Elise Landais, James C Paulson, Ian A Wilson, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes...
June 12, 2018: Cell Reports
https://www.readbyqxmd.com/read/29890181/prevalence-and-risk-factors-of-antibodies-to-human-leukocyte-antigens-in-haploidentical-stem-cell-transplantation-candidates-a-multi-center-study
#7
Ming-Rui Huo, Ya-Jing Xu, Shu-Zhen Zhai, Meng Lv, Yu Wang, Le-Qing Cao, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Hua Yan, Fei-Fei Tang, Xiao-Dong Mo, Ming-Feng Zhao, Kai-Yan Liu, Xiao-Jun Huang, Ying-Jun Chang
We investigated the prevalence of and risk factors for antibodies to HLA in 1,663 haploidentical transplant candidates. Among these cases, 349 (21.0%) showed positive panel-reactive antibody (PRA) either for class I or class II HLA. Multivariate analysis showed the following: i) risk factors associated with the prevalence of PRA either for class I or class II HLA were female gender (P=0.018), prior transfusions (P<0.001) or pregnancy (P<0.001), and cases with MDS (P=0.018); compared to other patients, subjects with ALL had a lower prevalence of class I antibodies (P=0...
June 8, 2018: Human Immunology
https://www.readbyqxmd.com/read/29889829/humoral-and-cellular-immune-responses-to-yersinia-pestis-pla-antigen-in-humans-immunized-with-live-plague-vaccine
#8
Valentina A Feodorova, Anna M Lyapina, Maria A Khizhnyakova, Sergey S Zaitsev, Lidiya V Sayapina, Tatiana E Arseneva, Alexey L Trukhachev, Svetlana A Lebedeva, Maxim V Telepnev, Onega V Ulianova, Elena P Lyapina, Sergey S Ulyanov, Vladimir L Motin
BACKGROUND: To establish correlates of human immunity to the live plague vaccine (LPV), we analyzed parameters of cellular and antibody response to the plasminogen activator Pla of Y. pestis. This outer membrane protease is an essential virulence factor that is steadily expressed by Y. pestis. METHODOLOGY/PRINCIPAL FINDINGS: PBMCs and sera were obtained from a cohort of naïve (n = 17) and LPV-vaccinated (n = 34) donors. Anti-Pla antibodies of different classes and IgG subclasses were determined by ELISA and immunoblotting...
June 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29888557/persistence-of-de-novo-donor-specific-hla-antibodies-after-lung-transplantation-a-potential-marker-of-decreased-patient-survival
#9
M Schmitzer, H Winter, N Kneidinger, G Meimarakis, A Dick, R Schramm, L V Klotz, G Preissler, N Strobl, V von Dossow, C Schneider, T Weig, R Hatz, T Kauke
The impact of de novo donor-specific anti-HLA antibodies (DSA) on outcomes in lung transplantation is still a matter of debate. We hypothesize that differentiating DSA by persistent and transient appearance may offer an additional risk assessment. The clinical relevance of HLA-antibodies was investigated prospectively in 72 recipients with a median follow-up period of 21 months. The presence of HLA-antibodies was analysed by single antigen bead assay prior to and after (3 weeks, 3, 6, 12 and 18 months) transplantation...
June 10, 2018: HLA
https://www.readbyqxmd.com/read/29888023/absence-of-rejection-in-a-facial-allograft-recipient-with-a-positive-flow-crossmatch-24-months-after-induction-with-rabbit-anti-thymocyte-globulin-and-anti-cd20-monoclonal-antibody
#10
Bruce E Gelb, J Rodrigo Diaz-Siso, Natalie M Plana, Adam Jacoby, William J Rifkin, Kimberly S Khouri, Daniel J Ceradini, Eduardo D Rodriguez
Background: Donor-specific antibodies (DSA) to human leukocyte antigen increase the risk of accelerated rejection and allograft damage and reduce the likelihood of successful transplantation. Patients with full-thickness facial burns may benefit from facial allotransplantation. However, they are at a high risk of developing DSA due to standard features of their acute care. Case Presentation: A 41-year-old male with severe disfigurement from facial burns consented to facial allotransplantation in 2014; panel reactive antibody score was 0%...
2018: Case Reports in Transplantation
https://www.readbyqxmd.com/read/29885443/value-of-c3d-assay-and-igg-subclass-in-the-prediction-of-the-flow-cytometry-cross-match-result-for-renal-transplantation
#11
Alan G Contreras, Aurora Casillas-Abundis, Josefina Alberú, Luis Llorente, Guadalupe Lima, Adriana Arvizu, Adrián de Santiago, Mario Vilatobá, Julio Granados, Luis E Morales-Buenrostro, Rodrigo Cruz, José M Arreola-Guerra
The aim of this study is to compare the association and the predictive capacity of DSA MFI, complement fixing capacity (C3d assay) and IgG subclasses determination in the prediction of FCxM result. METHODS: We used cryopreserved (70C) sera from potential renal transplant recipients, containing DSA against their respective potential donors. All patients showed negative AHG-CDC CxM and either positive or negative FCxM. Class I and Class II HLA-DSA were determined by Luminex SAB. C3d were detected by luminex (Lifecodes®Immucor), DSA IgG 1-4 subclasses were evaluated using monoclonal antibodies specific for IgG subclasses (Luminex)...
June 6, 2018: Transplant Immunology
https://www.readbyqxmd.com/read/29880346/correlation-between-the-transplant-evaluation-rating-scale-ters-and-medical-outcomes-in-living-donor-kidney-transplant-recipients-a-retrospective-analysis
#12
G Dieplinger, N Mokhaberi, R Wahba, S Peltzer, D Buchner, H A Schlösser, V Ditt, A von Borstel, U Bauerfeind, U Lange, W Arns, C Kurschat, H A Stippel, F Vitinius
BACKGROUND: Pretransplant psychosocial evaluation of living-donor kidney transplantation (LDKT) candidates identifies recipients with potentially inferior posttransplant outcomes. Rating instruments, based on semi-standardized interviews, help to improve and standardize psychosocial evaluation. The goal of this study was to retrospectively investigate the correlation between the Transplant Evaluation Rating Scale (TERS) and transplant outcome in LDKT recipients. METHODS: TERS scores were retrospectively generated by 2 raters based on comprehensive interviews of 146 LDKT recipients conducted by mental health professionals (interrater reliability, 0...
June 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29878122/increased-cd40l-pd-1-follicular-helper-t-cell-tfh-as-a-biomarker-for-predicting-calcineurin-inhibitor-sensitivity-against-tfh-mediated-b-cell-activation-antibody-production-after-kidney-transplantation
#13
Kenta Iwasaki, Nana Kitahata, Takahisa Hiramitsu, Takayuki Yamamoto, Takayuki Noda, Manabu Okada, Shunji Narumi, Yoshihiko Watarai, Yuko Miwa, Kazuharu Uchida, Matsuoka Yutaka, Kosei Horimi, Takaaki Kobayashi
It is unclear to what extent follicular helper T-cell (Tfh) development and de novo donor specific HLA antibody (DSA) production could be influenced by immunosuppressive agents, particularly calcineurin inhibitor (CNI), after kidney transplantation. Here, the effects of immunosuppressive agents on Tfh-mediated B-cell activation and antibody production were investigated. In vitro circulating Tfh (cTfh; memory CD4+CXCR5+)/B-cell (CD19+) co-culture assays revealed that CNI considerably inhibited cTfh-mediated B-cell activation and IgG antibody secretion through the suppression of IL-21 and IL-2...
June 7, 2018: International Immunology
https://www.readbyqxmd.com/read/29873420/multiple-miscarriages-in-two-sisters-of-thai-origin-with-the-rare-p-k-phenotype-caused-by-a-novel-nonsense-mutation-at-the-b3galnt1-locus
#14
J Ricci Hagman, A K Hult, J S Westman, B Hosseini-Maaf, P Jongruamklang, J Saipin, S Bejrachandra, M L Olsson
OBJECTIVES: To determine the genetic background underlying the Pk phenotype in two Thai sisters suffering from multiple spontaneous abortions. BACKGROUND: The P antigen is carried by globoside, an abundant glycosphingolipid in the red blood cell (RBC) membrane. Inactivating mutations in the 3-β-N-acetylgalactosaminyltransferase gene (B3GALNT1) give rise to the rare Pk phenotype, which lack the P and PX2 antigens. Consequently, naturally occurring anti-P may cause recurrent miscarriages following the cytotoxic attack of the globoside-rich fetal portion of the placenta...
June 6, 2018: Transfusion Medicine
https://www.readbyqxmd.com/read/29868492/high-level-antibody-response-to-pandemic-influenza-h1n1-09-virus-is-associated-with-interferon-induced-transmembrane-protein-3-rs12252-cc-in-young-adults
#15
Ling Qin, Dayan Wang, Dongfu Li, Yan Zhao, Yanchun Peng, Dannielle Wellington, Yanchao Dai, Huanqin Sun, Jinping Sun, Guihai Liu, Andrew McMichael, Tao Dong, Yonghong Zhang
Background: The C allele of the interferon-induced transmembrane protein-3 ( IFITM3 ) SNP rs12252, a common allele in South East Asia and China, is strongly associated with severe influenza infection. However, despite the high occurrence of rs12252-CC genotype in Chinese population (~25%), severe influenza infection is rare. The aim of study is to determine whether rs12252-CC individuals have pre-existing antibody responses to previous seasonal influenza infections. Cohort and Method: A total 99 young healthy volunteers (18-20 years) were recruited and received an influenza seasonal Vaccination [A/Switzerland/9715293/2013(H3N2), A/California/7/2009 (pdm09H1N1) and B/Jeep/3073/2013-like virus (Flu-B)]...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29864460/improving-the-performance-of-virtual-crossmatch-results-by-correlating-with-nationally-performed-physical-crossmatches-obtaining-additional-value-from-proficiency-testing-activities
#16
Sean M Wrenn, Carlos E Marroquin, Donna-Sue Hain, Sarah Harm, Jaime Pineda, Paulette B Hammond, Diti H Shah, Susan E Hillyard, Mark Fung
PURPOSE: When donor specific HLA antibodies (DSA) are identified, the predictive value of whether a certain strength of reactivity (mean fluorescence intensity, MFI) leads to a positive crossmatch is uncertain. To determine this, we compared the DSA MFI results we generated locally for nationally distributed proficiency samples against the percentage of other laboratories reporting a positive crossmatch. METHOD: DSA MFI from single antigen beads reported by our laboratory for nationally-distributed proficiency testing survey samples was compared against the aggregate percentage of participating laboratories reporting the crossmatch positive using direct, antiglobulin-enhanced microcytotoxic (CDC-AHG), or flow cytometric methods from 2011 to 2015...
June 1, 2018: Human Immunology
https://www.readbyqxmd.com/read/29863579/donor-specific-antibody-surveillance-and-graft-outcomes-in-pediatric-kidney-transplant-recipients
#17
Rachel M Engen, Giulia E Park, Cooper S Schumacher, Idoia Gimferrer, Paul Warner, Laura S Finn, Noel S Weiss, Jodi M Smith
INTRODUCTION: The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear. METHODS: 103 patients <18 years old receiving a first, kidney alone transplant between 12/1/2007 and 12/31/2013 underwent DSA screening every 3 months for 2 years posttransplant, with additional testing as clinically indicated...
May 31, 2018: Transplantation
https://www.readbyqxmd.com/read/29863455/desensitization-in-the-setting-of-hla-incompatible-kidney-transplant
#18
REVIEW
Paolo Malvezzi, Thomas Jouve, Johan Noble, Lionel Rostaing
The number of kidney transplant candidates is increasing sharply. Among them, at least 20% are HLA sensitized. For these patients, in the setting of both living- and deceased-donor kidney transplant, we may face donor-specific alloantibodies at pretransplant. In such cases, the microlymphocytotoxicity crossmatch may or may not be positive. Kidney transplant with donor-specific antibodies at pretransplant is known as HLA-incompatible transplant. At present, we can use many methods to ensure that the kidney transplant is successful, provided that the recipient is desensitized before or after transplant...
June 1, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29862642/another-piece-of-the-antibody-puzzle-observations-from-the-halt-study
#19
EDITORIAL
Laurie D Snyder, Kathryn J Tinckam
In the rapidly evolving domain of clinical transplantation immunobiology, the interrogation and interpretation of HLA antibodies and their associated clinical consequences are in the spotlight. In lung transplant, HLA antibodies, in particular donor specific antibodies (DSA), are a determining component of the lung transplant antibody mediated rejection (AMR) definition (1). DSA after lung transplant are widely regarded as poor prognosticator, though sparse data to date necessitate ongoing discourse and continued investigation into incidence, timing and treatment...
June 4, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29861170/multi-donor-longitudinal-antibody-repertoire-sequencing-reveals-the-existence-of-public-antibody-clonotypes-in-hiv-1-infection
#20
Ian Setliff, Wyatt J McDonnell, Nagarajan Raju, Robin G Bombardi, Amyn A Murji, Cathrine Scheepers, Rutendo Ziki, Charissa Mynhardt, Bryan E Shepherd, Alusha A Mamchak, Nigel Garrett, Salim Abdool Karim, Simon A Mallal, James E Crowe, Lynn Morris, Ivelin S Georgiev
Characterization of single antibody lineages within infected individuals has provided insights into the development of Env-specific antibodies. However, a systems-level understanding of the humoral response against HIV-1 is limited. Here, we interrogated the antibody repertoires of multiple HIV-infected donors from an infection-naive state through acute and chronic infection using next-generation sequencing. This analysis revealed the existence of "public" antibody clonotypes that were shared among multiple HIV-infected individuals...
May 28, 2018: Cell Host & Microbe
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