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Donor specific antibodies

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https://www.readbyqxmd.com/read/27913515/cellular-immune-responses-in-red-blood-cell-alloimmunization
#1
James C Zimring, Krystalyn E Hudson
In excess of 340 blood group antigens have now been described that vary between individuals. Thus, any unit of blood that is nonautologous represents a significant dose of alloantigen. Most blood group antigens are proteins, which differ by a single amino acid between donors and recipients. Approximately 1 out of every 70 individuals are transfused each year (in the United States alone), which leads to antibody responses to red blood cell (RBC) alloantigens in some transfusion recipients. When alloantibodies are formed, in many cases, RBCs expressing the antigen in question can no longer be safely transfused...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27907066/b-cell-based-seamless-engineering-of-antibody-fc-domains
#2
Koji Hashimoto, Kohei Kurosawa, Akiho Murayama, Hidetaka Seo, Kunihiro Ohta
Engineering of monoclonal antibodies (mAbs) enables us to obtain mAbs with additional functions. In particular, modifications in antibody's Fc (fragment, crystallizable) region can provide multiple benefits such as added toxicity by drug conjugation, higher affinity to Fc receptors on immunocytes, or the addition of functional modules. However, the generation of recombinant antibodies requires multiple laborious bioengineering steps. We previously developed a technology that enables rapid in vitro screening and isolation of specific mAb-expressing cells from the libraries constructed with chicken B-cell line DT40 (referred to as the 'ADLib system')...
2016: PloS One
https://www.readbyqxmd.com/read/27906829/evidence-for-cd16a-mediated-nk-cell-stimulation-in-antibody-mediated-kidney-transplant-rejection
#3
Michael D Parkes, Philip F Halloran, Luis G Hidalgo
BACKGROUND: Natural killer (NK) cells localize in the microcirculation in antibody-mediated rejection (ABMR) and have been postulated to be activated by donor-specific anti-HLA antibodies triggering their CD16a Fc receptors. However, direct evidence for NK cell CD16a triggering in ABMR is lacking. We hypothesized that CD16a-inducible NK cell-selective transcripts would be expressed in human ABMR biopsies and would offer evidence for CD16a triggering. METHODS: We stimulated human NK cells through CD16a in vitro, characterized CD16a-inducible transcripts, and studied their expression in human kidney transplant biopsies with ABMR and in an extended human cell panel to determine their selectivity...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27905683/prolonged-neutropenia-due-to-antihuman-neutrophil-antigen-2-cd177-antibody-after-bone-marrow-transplantation
#4
Taizo Wada, Satoshi Miyamoto, Hiroyuki Okamoto, Yusuke Matsuda, Tomoko Toma, Kohsuke Imai, Masatoshi Takagi, Tomohiro Morio, Akihiro Yachie
We describe a patient who presented with prolonged neutropenia due to anti-human neutrophil antigen (HNA)-2 (CD177) antibody after allogeneic bone marrow transplantation. A granulocyte immunofluorescence test showed bimodal expression of antineutrophil antibody that resulted from specific binding of anti-HNA-2 to CD177(+) neutrophils from healthy donors. The patient did not respond to granulocyte colony stimulating factor, which is able to upregulate CD177 expression on neutrophils. The low percentage of CD177(+) cells in the few remaining neutrophils supports the possibility of elimination of CD177-upregulated neutrophils...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27903981/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#5
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900974/disseminated-mycobacteria-chelonae-infection-in-a-kidney-pancreas-transplant-recipient-a-case-report-and-review-of-the-literature
#6
Shafi Malik, Ananda Ghosh, Shahid Husain
A 40-year-old male with a long-standing history of type 1 diabetes with end-stage renal failure underwent combined kidney-pancreas (KP) transplant from a standard criteria donor. Post-operative course was uncomplicated with good primary function of both transplant grafts. Induction was with thymoglobulin and maintenance immunosuppression was with tacrolimus, mycophenolate mofetil and prednisolone. Nine weeks post-transplant, the patient developed dysfunction of both grafts. Panel reactive antibody testing revealed that the patient had developed a de novo donor-specific antibody and considering an antibody-mediated rejection the patient was treated with intravenous pulse methyl prednisone 500 mg ×3 doses, IV immunoglobulin 2 mg/kg in two divided doses, and ATG 7 mg/kg (total dose of 700 mg)...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27898462/recent-advances-in-allograft-vasculopathy
#7
Jonathan Merola, Daniel D Jane-Wit, Jordan S Pober
PURPOSE OF REVIEW: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. RECENT FINDINGS: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA)...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27894836/use-of-complement-binding-assays-to-assess-the-efficacy-of-antibody-mediated-rejection-therapy-and-prediction-of-graft-survival-in-kidney-transplantation
#8
Daniel S Ramon, Yihung Huang, Lili Zhao, TrisAnn Rendulic, Jeong M Park, Randall S Sung, Milagros Samaniego
BACKGROUND: The Luminex(®) single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR...
November 25, 2016: Human Immunology
https://www.readbyqxmd.com/read/27893614/the-presence-of-pretransplant-hla-antibodies-does-not-impact-the-development-of-chronic-lung-allograft-dysfunction-or-clad-related-death
#9
Oscar E Zazueta, Sara E Preston, Anna Moniodis, Sabrina Fried, Miae Kim, Keri Townsend, Isabelle Wood, Steve Boukedes, Indira Guleria, Phillip Camp, Souheil El-Chemaly, Ivan O Rosas, Anil Chandraker, Edgar Milford, Hilary J Goldberg
BACKGROUND: Development of Donor-specific Antibodies (DSA) after lung transplantation is associated with antibody mediated rejection (AMR), acute cellular rejection, and bronchiolitis obliterans syndrome (BOS); however, the significance of circulating antibodies before transplant remains unclear. METHODS: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012.We assessed the impact of circulating human leukocyte (HLA) and noncytotoxic Donor Specific antibodies (DSA) detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD related death...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27893347/asymptomatic-infections-in-blood-donors-harbouring-plasmodium-an-invisible-risk-detected-by-molecular-and-serological-tools
#10
Giselle F M C Lima, Maria C Arroyo Sanchez, José E Levi, Mahyumi Fujimori, Luiza Da Cruz Caramelo, Arianni Rondelli Sanchez, Eduardo M Ramos-Sanchez, Juliana Inoue, Maria De Jesus Costa-Nascimento, Alfredo Mendrone Junior, Silvia M Di Santi
BACKGROUND: Transfusion-transmitted malaria due to asymptomatic Plasmodium infections is a challenge for blood banks. There is a lack of data on the prevalence of asymptomatic infected blood donors and the incidence of transfusion-transmitted malaria in low endemicity areas worldwide. We estimated the frequency of blood donors harbouring Plasmodium in an area in which asymptomatic infections have been reported. MATERIAL AND METHODS: To estimate the frequency of blood donors harbouring Plasmodium we used microscopy and molecular tools...
November 7, 2016: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/27888573/b-cell-activating-factor-baff-a-predictor-of-antibody-mediated-rejection-in-kidney-transplantation-recipients
#11
Wannarat Pongpirul, Wiwat Chancharoenthana, Krit Pongpirul, Asada Leelahavanichakul, Wipawee Kittikowit, Kamonwan Jutivorakool, Bunthoon Nonthasoot, Yingyos Avihingsanon, Somchai Eiam-Ong, Kearkiat Praditpornsilpa, Natavudh Townamchai
BACKGROUND: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection...
November 26, 2016: Nephrology
https://www.readbyqxmd.com/read/27887647/the-hide-and-seek-of-plasmodium-vivax-in-west-africa-report-from-a-large-scale-study-in-beninese-asymptomatic-subjects
#12
Philippe Poirier, Cécile Doderer-Lang, Pascal S Atchade, Jean-Philippe Lemoine, Marie-Louise Coquelin de l'Isle, Ahmed Abou-Bacar, Alexander W Pfaff, Julie Brunet, Lydia Arnoux, Elodie Haar, Denis Filisetti, Sylvie Perrotey, Nicodeme W Chabi, Casimir D Akpovi, Ludovic Anani, André Bigot, Ambaliou Sanni, Ermanno Candolfi
BACKGROUND: Plasmodium vivax is considered to be absent from western Africa, where the prevalence of Duffy-negative red blood cell phenotype proves to be high. Several studies have, however, detected P. vivax infection cases in this part of Africa, raising the question of what is the actual prevalence of P. vivax in local populations. METHODS: The presence of P. vivax was investigated in a large population of healthy blood donors in Benin using microscopy, serology and molecular detection...
November 25, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27872835/six-end-stage-renal-disease-patients-benefited-from-first-non-simultaneous-single-center-6-way-kidney-exchange-transplantation-in-india
#13
Vivek B Kute, Himanshu V Patel, Umesh T Varyani, Pankaj R Shah, Pranjal R Modi, Veena R Shah, Sayyed J Rizvi, Bipin C Pal, Priya S Shah, Pavan S Wakhare, Vijay A Ghodela, Saiprasad G Shinde, Varsha B Trivedi, Minaxi H Patel, Hargovind L Trivedi
AIM: To avoid desensitization protocols and ABO incompatible kidney transplantation (KT) due to high costs and increased risk of infections from intense immunosuppression. METHODS: We present institutional ethical review board - approved study of single center 6-way kidney exchange transplantation. The participants comprised ABO incompatibility (n = 1); positive cross-match and/or presence of donor specific antibody (n = 5). The average time required from registration in kidney paired donation (KPD) registry to find suitable donors was 45 d and time required to perform transplants after legal permission was 2 mo...
November 6, 2016: World Journal of Nephrology
https://www.readbyqxmd.com/read/27871759/rabbit-atg-or-basiliximab-induction-for-rapid-steroid-withdrawal-after-renal-transplantation-harmony-an-open-label-multicentre-randomised-controlled-trial
#14
Oliver Thomusch, Michael Wiesener, Mirian Opgenoorth, Andreas Pascher, Rainer Peter Woitas, Oliver Witzke, Bernd Jaenigen, Markus Rentsch, Heiner Wolters, Thomas Rath, Tülay Cingöz, Urs Benck, Bernhard Banas, Christian Hugo
BACKGROUND: Standard practice for immunosuppressive therapy after renal transplantation is quadruple therapy using antibody induction, low-dose tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake significantly increases cardiovascular risk factors with negative effects on the outcome, especially post-transplantation diabetes associated with morbidity and mortality. In this trial, we examined the efficacy and safety parameters of rapid steroid withdrawal after induction therapy with either rabbit antithymocyte globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during the first year after kidney transplantation...
November 18, 2016: Lancet
https://www.readbyqxmd.com/read/27870356/clinical-and-immunological-relevance-of-antibodies-in-solid-organ-transplantation
#15
REVIEW
N K Mehra, A K Baranwal
The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection...
December 2016: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/27869292/model-based-investigation-of-intracellular-processes-determining-antibody-fc-glycosylation-under-mild-hypothermia
#16
Si Nga Sou, Philip M Jedrzejewski, Ken Lee, Christopher Sellick, Karen M Polizzi, Cleo Kontoravdi
Despite the positive effects of mild hypothermic conditions on monoclonal antibody (mAb) productivity (qmAb ) during mammalian cell culture, the impact of reduced culture temperature on mAb Fc-glycosylation and the mechanism behind changes in the glycan composition is not fully established. The lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimisation. To address this issue, a mathematical model that quantitatively describes CHO cell behaviour and metabolism, mAb synthesis and its N-linked glycosylation profiles before and after the induction of mild hypothermia is constructed using two sets of parameters...
November 21, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27864476/anti-hinge-antibodies-recognize-igg-subclass-and-protease-restricted-neoepitopes
#17
Willem J J Falkenburg, Dirkjan van Schaardenburg, Pleuni Ooijevaar-de Heer, Michel W P Tsang-A-Sjoe, Irene E M Bultink, Alexandre E Voskuyl, Arthur E H Bentlage, Gestur Vidarsson, Gertjan Wolbink, Theo Rispens
Anti-hinge Abs (AHAs) target neoepitopes exposed after proteolytic cleavage of IgG. In this study, we explored the diversity of protease- and IgG subclass-restricted AHAs and their potential as immunological markers in healthy donors (HDs) and patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). AHA reactivity against IgG-degrading enzyme of Streptococcus pyogenes (IdeS)- or pepsin-generated F(ab')2 fragments of all four human IgG subclasses was determined. AHA reactivity against one or more out of eight F(ab')2 targets was found in 68% (68 of 100) of HDs, 69% (68 of 99) of SLE patients, and 81% (79 of 97) of RA patients...
November 18, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864153/immunogenicity-of-murine-mpeg-red-blood-cells-and-the-risk-of-anti-peg-antibodies-in-human-blood-donors
#18
Yevgeniya Le, Wendy M Toyofuku, Mark D Scott
The immunocamouflage of non-ABO blood group antigens by membrane grafted mPEG may attenuate the risk of RBC alloimmunization. However, concerns have been raised as to the immunogenic risk of PEG and PEG-RBC. To assess these risks, murine and human studies were done. Mice were exposed to soluble PEG prior to, or between, multiple transfusions (∼60 day intervals) of control or mPEG-RBC and cell survival was determined by flow cytometry. In some studies, the control and mPEG-RBC groups were reversed following one or more transfusions...
November 15, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27862883/the-banff-2015-kidney-meeting-report-current-challenges-in-rejection-classification-and-prospects-for-adopting-molecular-pathology
#19
A Loupy, M Haas, K Solez, L Racusen, D Glotz, D Seron, B J Nankivell, R B Colvin, M Afrouzian, E Akalin, N Alachkar, S Bagnasco, J U Becker, L Cornell, C Drachenberg, D Dragun, H De Kort, I W Gibson, E S Kraus, C Lefaucheur, C Legendre, H Liapis, T Muthukumar, V Nickeleit, B Orandi, W Park, M Rabant, P Randhawa, E F Reed, C Roufosse, S V Seshan, B Sis, H K Singh, C Schinstock, A Tambur, A Zeevi, M Mengel
The XIII. Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection, requires further consensus agreement and validation in biopsies...
November 10, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862486/characterisation-of-maternal-human-leukocyte-antigen-class-i-antibodies-in-suspected-foetal-and-neonatal-alloimmune-thrombocytopenia
#20
E Refsum, A Mörtberg, J Dahl, S Meinke, M-K Auvinen, M Westgren, M Reilly, P Höglund, A Wikman
OBJECTIVES: To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). BACKGROUND: FNAIT occurs in 1 : 1-2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. MATERIAL AND METHODS: A total of 260 patient samples were referred between 2007 and 2012...
November 9, 2016: Transfusion Medicine
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