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Panel reactive antibody

Tomas Lorant, Mats Bengtsson, Torsten Eich, Britt-Marie Eriksson, Lena Winstedt, Sofia Järnum, Yvonne Stenberg, Anna-Karin Robertson, Kristina Mosén, Lars Björck, Lars Bäckman, Erik Larsson, Kathryn Wood, Gunnar Tufveson, Christian Kjellman
Safety, immunogenicity, pharmacokinetics and efficacy of the immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS, Imlifidase) was assessed in a single centre, open label ascending dose study in highly sensitised chronic kidney disease patients. Eight patients with cytotoxic panel-reactive antibodies (median cytotoxic PRA of 64%) at enrolment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight x2 (n=3); 0.25 mg/kg x1 (n=3) or 0.25 mg/kg x2 (n=2)). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days...
March 21, 2018: American Journal of Transplantation
Minghua Zheng, Jie Jiang, Xiao Zhang, Nan Wang, Kaihang Wang, Qiong Li, Tingting Li, Qingshan Lin, Yingbin Wang, Hai Yu, Ying Gu, Jun Zhang, Shaowei Li, Ningshao Xia
Hepatitis E virus (HEV) is associated with acute hepatitis disease. Numerous truncated HEV capsid proteins have been successfully expressed using different expression systems. Among these, p495, a protein truncated at its N- and C-termini by 111 and 54 amino acids (aa), respectively (HEV ORF2 aa 112-606) can self-assemble into T = 1 virus-like particles (VLPs) when expressed by insect cells. A shorter p239 (aa 368-606) protein is a particulate antigen that we have previously used in our commercialized HEV vaccine, Hecolin...
March 12, 2018: Vaccine
M Lyu, N Cha, Y F Zou, J H Leng, L Xu, Y Sun, Y Y Hao
Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells...
March 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Ji Eun Park, Chi Young Kim, Moo Suk Park, Joo Han Song, Young Sam Kim, Jin Gu Lee, Hyo Chae Paik, Song Yee Kim
BACKGROUND: Previous studies have suggested that antibodies against human leukocyte antigen (HLA) are associated with worse outcomes in lung transplantation. However, little is known about the factors associated with outcomes following lung transplantation in Asia. Accordingly, we investigated the prevalence of anti-HLA antibodies in recipients before transplantation and assessed their impact on outcomes in Korea. METHODS: A single-center retrospective study was conducted...
March 12, 2018: BMC Pulmonary Medicine
Oluwatoyosi A Onwuemene, Steven C Grambow, Chetan B Patel, Robert J Mentz, Carmelo A Milano, Joseph G Rogers, Ara D Metjian, Gowthami M Arepally, Thomas L Ortel
INTRODUCTION: Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation. METHODS: In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical Center from 2010 to 2014, we reviewed 3 TPE treatment patterns: a Single TPE procedure within 24 h of transplant; Multiple TPE procedures initiated within 24 h of transplant; and 1 or more TPE procedures beginning >24 h post-transplant...
March 10, 2018: Journal of Clinical Apheresis
Geraldine Miller, Heidi Schaefer, Sandra Yoder, Rachel Miller, Patricia Winokur, Karen Kotloff, David Klassen, Michael Wierzbicki, Cyrille Amegashie, Kathryn Edwards
BACKGROUND: Solid organ transplant recipients are at increased risk for reactivation of herpes zoster, or shingles, and have a higher frequency of serious complications including post-herpetic neuralgia. A live, attenuated shingles vaccine is effective and approved for individuals 50 years and older. The vaccine is contraindicated following transplantation but may be used in patients with renal failure. Utilization of the vaccine has been poor in patients with end-stage renal disease, including those awaiting transplant, due to concerns for safety, efficacy, and potential sensitization prior to transplant...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Rebekah C Kading, Robert M Kityo, Eric C Mossel, Erin M Borland, Teddie Nakayiki, Betty Nalikka, Luke Nyakarahuka, Jeremy P Ledermann, Nicholas A Panella, Amy T Gilbert, Mary B Crabtree, Julian Kerbis Peterhans, Jonathan S Towner, Brian R Amman, Tara K Sealy, Stuart T Nichol, Ann M Powers, Julius J Lutwama, Barry R Miller
Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT)...
2018: Infection Ecology & Epidemiology
Adam Vigil, Angeles Estélles, Lawrence M Kauvar, Scott K Johnson, Ralph A Tripp, Michael Wittekind
Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single cell screening technology to identify rare monoclonal antibodies (mAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 mAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 mAbs, three exhibited low expression in a transient transfection system, four were neutralizers that bound to the HA head region, eleven were stalk-binding non-neutralizers, and five were stalk-binding neutralizers with four of these five representing unique antibody sequences...
March 5, 2018: Antimicrobial Agents and Chemotherapy
M Giuliani, E Bartolini, B Galli, L Santini, P Lo Surdo, F Buricchi, M Bruttini, B Benucci, N Pacchiani, L Alleri, D Donnarumma, W Pansegrau, I Peschiera, I Ferlenghi, R Cozzi, N Norais, M M Giuliani, D Maione, M Pizza, R Rappuoli, O Finco, V Masignani
4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized...
February 27, 2018: Scientific Reports
Martin Andreas, Kathrin Freystaetter, Martin H Bernardi, Andreas Zuckermann
A 31-year-old male patient underwent a heart transplantation due to dilated cardiomyopathy. He experienced accelerated acute antibody-mediated rejection despite being negative for human leukocyte antigen antibodies (0% panel-reactive antibodies prior to surgery). Further assessment revealed a common antigen between a homograft implanted 17 years earlier during the Ross procedure and the heart donor. The homograft likely induced specific antibody formation. Interestingly, panel-reactive antibody levels measured 7 years prior to transplantation were 7%...
February 21, 2018: European Journal of Cardio-thoracic Surgery
Jarrod J Mousa, Elad Binshtein, Stacey Human, Rachel H Fong, Gabriela Alvarado, Benjamin J Doranz, Martin L Moore, Melanie D Ohi, James E Crowe
Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years of age. The RSV fusion (F) protein is a primary target of human antibodies, and it has several antigenic regions capable of inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre-fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV have been described that bind and neutralize both RSV and human metapneumovirus (hMPV). To explore the diversity of binding modes at antigenic site IV, we generated a panel of four new human monoclonal antibodies (mAbs) and competition-binding suggested the mAbs bind at antigenic site IV...
February 2018: PLoS Pathogens
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
Mahiuddin Ahmed, Andres Lopez-Albaitero, Dmitry Pankov, Brian H Santich, Hong Liu, Su Yan, Jingyi Xiang, Pei Wang, Aisha N Hasan, Annamalai Selvakumar, Richard J O'Reilly, Cheng Liu, Nai-Kong V Cheung
EBV infection is associated with a number of malignancies of clinical unmet need, including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and posttransplant lymphoproliferative disease (PTLD), all of which express the EBV protein latent membrane protein 2A (LMP2A), an antigen that is difficult to target by conventional antibody approaches. To overcome this, we utilized phage display technology and a structure-guided selection strategy to generate human T cell receptor-like (TCR-like) monoclonal antibodies with exquisite specificity for the LMP2A-derived nonamer peptide, C426LGGLLTMV434 (CLG), as presented on HLA-A*02:01...
February 22, 2018: JCI Insight
Namita Singh, Ana P Rossi, Marizela Savic, Ronald J Rubocki, Mark G Parker, John P Vella
Background: Rabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line. Methods: We theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg/kg) is safe and effective, leading to development of a risk-stratified treatment protocol...
February 2018: Transplantation Direct
Paneerselvam Nandagopal, Jayanta Bhattacharya, Aylur K Srikrishnan, Rajat Goyal, Chinnambedu Ravichandran Swathirajan, Shilpa Patil, Shanmugam Saravanan, Suprit Deshpande, Ramachandran Vignesh, Sunil Suhas Solomon, Nikhil Singla, Joyeeta Mukherjee, Kailapuri G Murugavel
Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention...
February 5, 2018: Journal of General Virology
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
Tripti Shrivastava, Sweety Samal, Ashish K Tyagi, Sandeep Goswami, Naresh Kumar, Gabriel Ozorowski, Andrew B Ward, Bimal K Chakrabarti
Using HIV-1 envelope protein (Env)-based immunogens that closely mimic the conformation of functional HIV-1 Envs and represent the isolates prevalent in relevant geographical region is considered a rational approach towards developing HIV vaccine. We recently reported that like clade B Env, JRFL, membrane bound Indian clade C Env, 4-2.J41 is also efficiently cleaved and displays desirable antigenic properties for plasmid DNA immunization. Here, we evaluated the immune response in rabbit by injecting the animals with plasmid expressing membrane bound efficiently cleaved 4-2...
February 8, 2018: Vaccine
Thomas Schachtner, Natalie M Otto, Maik Stein, Petra Reinke
Background: The number of kidney transplant recipients (KTRs) being waitlisted for a subsequent transplantation has disproportionately increased to almost 25%. Evidence for the optimal management of the failed allograft, however, remains inconsistent. Methods: We studied 111 KTRs who underwent their second kidney transplantation from 1998 to 2015. In 51/111 KTRs (46%) the failed allograft was removed and in 60/111 (54%) the failed allograft was retained. KTRs with primary non-function and allograft loss <12  months of the first failed allograft were excluded from analysis...
February 1, 2018: Nephrology, Dialysis, Transplantation
Ziyad M Binsalamah, Juan Marcano, Rodrigo Zea-Vera, Hari Tunuguntla, Debra L Kearney, Jeffrey S Heinle, Charles D Fraser, Carlos M Mery
Graft rejection is the most common factor that limits graft survival after transplantation. During infancy, the humoral immune system is partially suppressed and humoral rejection of a cardiac allograft has not been reported in the absence of risk factors such as prior transplantation, blood transfusions, ventricular assist devices, and elevation of panel reactive antibodies. We present a case of an infant with dilated cardiomyopathy who developed multiple episodes of acute humoral rejection after heart transplantation in the absence of risk factors...
February 4, 2018: Journal of Cardiac Surgery
Maurilia Marcacci, Serena Sant, Iolanda Mangone, Maria Goria, Alessandro Dondo, Simona Zoppi, René G P van Gennip, Maria Cristina Radaelli, Cesare Cammà, Piet A van Rijn, Giovanni Savini, Alessio Lorusso
In this rapid communication, a novel atypical bluetongue virus (BTV) strain detected in goats in the Piedmont region (north-western Italy) is described. This strain, BTV-Z ITA2017, is most related in Seg-2/VP-2 (83.8% nt/82.7% aa) to strain TOV of BTV-25. Reactive antisera of goats positive by cELISA for BTV antibodies failed to neutralize a chimeric virus expressing the outermost protein of TOV. Infected animals displayed low levels of RNAemia and absence of clinical signs consistent with bluetongue infection, a scenario described in animals infected with atypical BTV strains...
February 2, 2018: Transboundary and Emerging Diseases
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