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https://www.readbyqxmd.com/read/28939750/inhibition-of-ebv-mediated-membrane-fusion-by-anti-ghgl-antibodies
#1
Karthik Sathiyamoorthy, Jiansen Jiang, Britta S Möhl, Jia Chen, Z Hong Zhou, Richard Longnecker, Theodore S Jardetzky
Herpesvirus entry into cells requires the coordinated action of multiple virus envelope glycoproteins, including gH, gL, and gB. For EBV, the gp42 protein assembles into complexes with gHgL heterodimers and binds HLA class II to activate gB-mediated membrane fusion with B cells. EBV tropism is dictated by gp42 levels in the virion, as it inhibits entry into epithelial cells while promoting entry into B cells. The gHgL and gB proteins are targets of neutralizing antibodies and potential candidates for subunit vaccine development, but our understanding of their neutralizing epitopes and the mechanisms of inhibition remain relatively unexplored...
September 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28939451/hla-haploidentical-stem-cell-transplant-with-pre-transplant-immunosuppression-for-patients-with-sickle-cell-disease
#2
Anna B Pawlowska, Jerry C Cheng, Nicole A Karras, Weili Sun, Leo D Wang, Alison D Bell, Lisa Gutierrez, Joseph Rosenthal
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD) but a significant number of patients lack a HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report, we describe a favorable haploidentical HCT approach in a limited cohort of sickle cell patients with significant co-morbidities...
September 19, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28930983/personalized-peptide-arrays-for-detection-of-hla-alloantibodies-in-organ-transplantation
#3
Pan Liu, Tomokazu Souma, Andrew Zu-Sern Wei, Xueying Xie, Xunrong Luo, Jing Jin
In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-HLA immunity, which presents either as pre-existing or de novo generated HLA antibodies that constitute a major transplantation barrier. Current tests are built on a single-antigen beads (SAB) platform using a fixed set of ~100 preselected recombinant HLA antigens to probe transplant sera...
September 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28926521/blockade-of-hla-antibody-triggered-classical-complement-activation-in-sera-from-subjects-dosed-with-the-anti-c1s-monoclonal-antibody-tnt009-results-from-a-randomized-first-in-human-phase-1-trial
#4
Jakob Mühlbacher, Bernd Jilma, Markus Wahrmann, Johann Bartko, Farsad Eskandary, Christian Schörgenhofer, Michael Schwameis, Graham C Parry, James C Gilbert, Sandip Panicker, Georg A Böhmig
BACKGROUND: Complement may play a key role in antibody-mediated rejection. A promising therapeutic approach may be classical pathway (CP) inhibition at the level of early component C1. METHODS: In this first-in-human, double-blind, randomized placebo-controlled phase 1 trial, we evaluated the safety and complement inhibitory effect of TNT009, a humanized monoclonal anti-C1s antibody. Sixty-four adult healthy volunteers received either single (n = 48; 7 consecutive cohorts, 0...
October 2017: Transplantation
https://www.readbyqxmd.com/read/28923614/flow-cytometry-panel-reactive-antibody-screening-of-anti-hla-antibodies-in-the-waiting-list-significantly-reduces-the-occurrence-of-acute-rejection-after-kidney-transplantation
#5
I Dedinská, N Mäčková, K Macháleková, J Miklušica, B Palkoci, J Fialová, M Čellár, P Galajda, M Mokáň
INTRODUCTION: The presence of preformed HLA-reactive antibodies in recipient serum before transplantation has long been recognized as a prominent risk factor for a generally worse graft outcome. Screening and identification of HLA antibodies can be used to stratify patients into high- and low-risk categories. MATERIALS AND METHODS: We determined patients' anti-HLA antibodies using flow cytometry panel-reactive antibody (flowPRA) screening, specifying more than 5% after positive screening...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28919518/depressed-serum-igm-levels-in-sle-are-restricted-to-defined-subgroups
#6
Caroline Grönwall, Uta Hardt, Johanna T Gustafsson, Kerstin Elvin, Kerstin Jensen-Urstad, Marika Kvarnström, Giorgia Grosso, Johan Rönnelid, Leonid Padykov, Iva Gunnarsson, Gregg J Silverman, Elisabet Svenungsson
Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/β2glycoprotein-I...
September 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28912774/therapeutic-antibodies-to-kir3dl2-and-other-target-antigens-on-cutaneous-t-cell-lymphomas
#7
REVIEW
Christian Schmitt, Anne Marie-Cardine, Armand Bensussan
KIR3DL2 is a member of the killer cell immunoglobulin-like receptor (KIR) family that was initially identified at the surface of natural killer (NK) cells. KIR3DL2, also known as CD158k, is expressed as a disulfide-linked homodimer. Each chain is composed of three immunoglobulin-like domains and a long cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs. Beside its expression on NK cells, it is also found on rare circulating T lymphocytes, mainly CD8(+). Although the KIR gene number varies between haplotype, KIR3DL2 is a framework gene present in all individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28910610/platelet-transfusion-refractoriness-in-patients-with-acute-myeloid-leukemia-treated-by-intensive-chemotherapy
#8
Thibault Comont, Suzanne Tavitian, Laurent Bardiaux, Marylise Fort, Bénédicte Debiol, Danièle Morère, Emilie Bérard, Eric Delabesse, Isabelle Luquet, Salima Martinez, Françoise Huguet, Christian Récher, Sarah Bertoli
Platelet transfusion refractoriness (PTR) is a major adverse event in the management of acute myeloid leukemia (AML). In a series of 897 adult patients with AML receiving intensive chemotherapy, we identified 41 patients (4.8%) with PTR. PTR was more frequently observed in parous women, patients with extra-medullary disease, a low white blood cell count, an infection, or hemophagocytic syndrome. Among the 31 patients with anti-human leucocyte antigen (HLA) antibodies, an HLA-matched donor was identified for 18 patients (58...
August 30, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28904429/correlation-of-pretransplant-donor-specific-antibody-assay-using-luminex-crossmatch-with-graft-outcome-in-renal-transplant-patients
#9
M Vimal, M P Chacko, G Basu, D Daniel
The significance of pretransplant anti-human leukocyte antigen antibody levels that are detectable by more sensitive platforms (including the Luminex platform) yet undetected by complement-dependent cytotoxicity (CDC) assay remains unclear. The aim of this study was to determine the clinical significance of the donor-specific antibody (DSA) assay Luminex crossmatch and its impact on short-term renal graft outcome such as acute rejections, graft survival, and graft function. The results of pretransplant DSA-lymphocyte crossmatching (LCXM) assay in 126 renal allograft recipients whose CDCs crossmatches were negative were retrospectively analyzed for correlation with posttransplant outcomes...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28894792/influence-of-hla-matching-on-the-efficacy-of-allogeneic-mesenchymal-stromal-cell-therapies-for-osteoarthritis-and-degenerative-disc-disease
#10
Javier García-Sancho, Ana Sánchez, Aurelio Vega, David C Noriega, Mercedes Nocito
BACKGROUND: The necessity for more effective therapies for chronic osteoarticular diseases has led to the development of treatments based on mesenchymal stem cells (MSCs), the natural precursors of musculoskeletal tissue. Treatments with autologous MSCs yielded excellent results, with nearly 70% improvement of pain and disability in osteoarthritis and degenerative disc disease. Using allogeneic MSCs is logistically more convenient and would widen the pool of eligible patients, but potential immune rejection should be considered...
September 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28894081/eculizumab-in-renal-transplantation-a-2017-update
#11
Ryszard Grenda, Magdalena Durlik
Despite ongoing progress in renal transplantation, there are still emerging challenges in this field, including consequences of ischemia-reperfusion injury (IRI), pre-existing and produced de novo anti-HLA donor-specific antibodies (DSA), and acute/chronic humoral rejection (AMR), as well as the recurrence of atypical hemolytic-uremic syndrome (aHUS) in genetically predisposed patients. All these conditions are related to the prominent role of the complement system and are deleterious to the fate of the renal graft...
September 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28883824/natural-killer-nk-cell-education-differentially-influences-hiv-antibody-dependent-nk-cell-activation-and-antibody-dependent-cellular-cytotoxicity
#12
REVIEW
Nicole F Bernard, Zahra Kiani, Alexandra Tremblay-McLean, Sanket A Kant, Christopher E Leeks, Franck P Dupuy
Immunotherapy using broadly neutralizing antibodies (bNAbs) endowed with Fc-mediated effector functions has been shown to be critical for protecting or controlling viral replication in animal models. In human, the RV144 Thai trial was the first trial to demonstrate a significant protection against HIV infection following vaccination. Analysis of the correlates of immune protection in this trial identified an association between the presence of antibody-dependent cellular cytotoxicity (ADCC) mediated by immunoglobulin G (IgG) antibodies (Abs) to HIV envelope (Env) V1/V2 loop structures and protection from infection, provided IgA Abs with competing specificity were not present...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28882445/strong-influence-of-human-leukocyte-antigen-dp-variants-on-response-to-hepatitis-b-vaccine-in-a-japanese-population
#13
Yuya Okada, Naoki Uno, Shuntaro Sato, Sayaka Mori, Daisuke Sasaki, Norihito Kaku, Kosuke Kosai, Yoshitomo Morinaga, Hiroo Hasegawa, Katsunori Yanagihara
Genome-wide association studies (GWASs) have reported that human leukocyte antigen (HLA) variants are associated with chronic hepatitis B, spontaneous hepatitis B virus (HBV) clearance, and response to hepatitis B vaccine. Single nucleotide polymorphisms (SNPs) in HLA-DP (rs9277535 and rs3077) and HLA-DQ (rs2856718 and rs7453920) have been repeatedly associated with chronic hepatitis B and spontaneous HBV clearance. However, the data on the SNPs associated with response to hepatitis B vaccine are inconclusive...
September 4, 2017: Vaccine
https://www.readbyqxmd.com/read/28881103/hla-polymorphisms-and-risk-of-red-blood-cell-alloimmunisation-in-polytransfused-patients-with-sickle-cell-anaemia
#14
C Rodrigues, A M Sell, G A S Guelsin, T T Higa, S Pagliarini E Silva, L C Macedo, E Â Sippert, J B de Alencar, Â Zanette, C R L Acorsi, L Castilho, J E L Visentainer
BACKGROUND: Red blood cell (RBC) alloimmunisation is an event that may occur due to factors such as numerous blood transfusions, age, gender and genetic factors such as human leukocyte antigen (HLA). AIMS/OBJECTIVES: The aim of the present study was to investigate the possibility of alloimmunisation to red blood cell group antigens associated with the HLA of individuals and to relate alloimmunisation to risk factors. METHODS: A total of 172 polytransfused patients with sickle cell anaemia (SCA) (44 alloimmunised, 128 non-alloimmunised) participated in this study...
September 7, 2017: Transfusion Medicine
https://www.readbyqxmd.com/read/28866981/carpal-spasm-in-a-girl-as-initial-presentation-of-celiac-disease-a-case-report
#15
Atifete Ramosaj-Morina, A Keka-Sylaj, V Hasbahta, A Baloku-Zejnullahu, M Azemi, R Zunec
BACKGROUND: Celiac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease. CASE PRESENTATION: We report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia...
September 4, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28865128/mechanisms-underlying-human-genetic-diversity-consequence-for-anti-graft-antibody-responses
#16
REVIEW
Roman Reindl-Schwaighofer, Andreas Heinzel, Lorenzo Signorini, Olivier Thaunat, Rainer Oberbauer
This review focuses on the emerging concept of genome-wide genetic variation as basis of an alloimmune response. Chronic antibody mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor specific alloantibodies is driven by indirect allorecognition of donor derived peptides representing a form of conventional T-cell response...
September 2, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28859622/neonatal-alloimmune-thrombocytopenia-caused-by-anti-hpa-antibodies-in-pregnant-chinese-women-a-study-protocol-for-a-multicentre-prospective-cohort-trial
#17
Li Chen, Zhiwei Liu, Tiemei Liu, Xianjun Ma, Meiying Rao, Yongjun Wang, Bo Sun, Wen Yin, Jun Zhang, Beizhan Yan, Xiaojuan Li, Qiushi Wang, Lei Zhang, Jun Wen, Fenghua Liu, Peng Wang, Yaming Wei, Yuanshuai Huang, Jiang Wu, Yi Guo, Yinlan Kang, Xiaochuan Song, Xiangfu Liu, Genling Zhang, Tingting Xie, Yonggeng Chen, Xiaojing Zeng, Zhongjun Li
BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT), caused by maternal antibodies raised against alloantigens carried on foetal platelets, is a very common haematological abnormality in newborns worldwide. However, baseline data on NAIT in China are lacking. Therefore, this study seeks to explore the incidence of alloantibody against the human platelet antigen (HPA) in pregnant women and its associations with NAIT in China. METHODS: A multicentre, prospective cohort study design will be used, and 55,497 pregnant women will be recruited for the first screening of the anti-HPA antibody at 12 to 28 weeks of gestational age...
August 31, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28857949/immune-mediated-necrotizing-myopathy-associated-with-statins-history-and-recent-developments
#18
Eleni Tiniakou, Lisa Christopher-Stine
PURPOSE OF REVIEW: The use of statins has increased exponentially over the last 2 decades. Consequently, side effects have also increased, with muscle-related side effects commonly reported. RECENT FINDINGS: Although once thought to be only associated with self-limited direct myotoxicity, statins have recently been described in association with an autoimmune myopathy in association with antibodies directed against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate limiting enzyme in cholesterol synthesis and the pharmacologic target of statins...
August 28, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28855662/tcr-like-antibodies-mediate-complement-and-antibody-dependent-cellular-cytotoxicity-against-epstein-barr-virus-transformed-b-lymphoblastoid-cells-expressing-different-hla-a-02-microvariants
#19
Junyun Lai, Joanna Ai Ling Choo, Wei Jian Tan, Chien Tei Too, Min Zin Oo, Manuel A Suter, Fatimah Bte Mustafa, Nalini Srinivasan, Conrad En Zuo Chan, Andrew Guo Xian Lim, Youjia Zhong, Soh Ha Chan, Brendon J Hanson, Nicholas R J Gascoigne, Paul A MacAry
Epstein-Barr virus (EBV) is a common gammaherpesvirus associated with various human malignancies. Antibodies with T cell receptor-like specificities (TCR-like mAbs) provide a means to target intracellular tumor- or virus-associated antigens by recognising their processed peptides presented on major histocompatibility complex (MHC) class I (pMHC) complexes. These antibodies are however thought to be relevant only for a single HLA allele. Here, we show that HLA-A*02:01-restricted EBV antigenic peptides EBNA1562-570, LMP1125-133 and LMP2A426-434 display binding degeneracy towards HLA-A*02 allelic microvariants, and that these pMHC complexes are recognised by anti-EBV TCR-like mAbs E1, L1 and L2 raised in the context of HLA-A*02:01...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838449/successful-blood-transfusion-management-of-a-living-donor-liver-transplant-recipient-in-the-presence-of-anti-jr-a-a-case-report
#20
N Kurata, Y Onishi, H Kamei, T Hori, M Komagome, C Kato, T Matsushita, Y Ogura
A 48-year-old Japanese woman was diagnosed with Budd-Chiari syndrome and transferred for possible living donor liver transplantation (LDLT). Examinations before LDLT revealed that the recipient had anti-Jr(a) and preformed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA). Rituximab was administrated at 16 days prior to the patient's scheduled LDLT for the prophylaxis of antibody-mediated rejection by DSA. The clinical significance of anti-Jr(a) has not been clearly established because of the rarity of this antibody, so we discussed blood transfusion strategy with the Department of Blood Transfusion Service and prepared for Jr(a)-negative packed red blood cells (RBCs)...
September 2017: Transplantation Proceedings
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