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https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#1
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28096513/targeting-tnfr2-with-antagonistic-antibodies-inhibits-proliferation-of-ovarian-cancer-cells-and-tumor-associated-tregs
#2
Heather Torrey, John Butterworth, Toshiyuki Mera, Yoshiaki Okubo, Limei Wang, Danielle Baum, Audrey Defusco, Sara Plager, Sarah Warden, Daniel Huang, Eva Vanamee, Rosemary Foster, Denise L Faustman
Major barriers to cancer therapy include the lack of selective inhibitors of regulatory T cells (Tregs) and the lack of broadly applicable ways to directly target tumors through frequently expressed surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is an attractive target protein because of its restricted abundance to highly immunosuppressive Tregs and oncogenic presence on human tumors. We characterized the effect of TNFR2 inhibition using antagonistic antibodies. In culture-based assays, we found that two TNFR2 antagonists inhibited Treg proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28095288/cytomegalovirus-immunoglobulin-g-avidity-index-among-blood-donors-in-alexandria-egypt
#3
Aleya Abdel Gawad, Mona Hashish, Amani Abaza, Aisha El-Kayal
BACKGROUND: Transfusion transmitted diseases (TTD) are a major challenge to transfusion services all over the world. Cytomegalovirus (CMV) is considered one of the main viruses associated with blood transfusion. As CMV screening is not included in routine screening tests done for donated blood in blood banks in Egypt, the detection of CMV Immunoglobulin G (IgG) avidity needs to be tested for being a useful tool to diagnose recent infection among blood donors. The aim of this work was to study CMV IgG avidity index (AI) among blood donors...
December 2016: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28092129/bortezomib-in-the-treatment-of-antibody-mediated-rejection-in-pediatric-kidney-transplant-recipients-a-multicenter-midwest-pediatric-nephrology-consortium-study
#4
Sarah Kizilbash, Donna Claes, Isa Ashoor, Ashton Chen, Sara Jandeska, Raed Bou Matar, Jason Misurac, Joseph Sherbotie, Katherine Twombley, Priya Verghese
Antibody-mediated rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of antibody-mediated rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven antibody-mediated rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients...
January 16, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28088367/assignment-of-c1q-binding-hla-antibodies-as-unacceptable-hla-antigens-avoids-positive-cdc-crossmatches-prior-to-transplantation-of-deceased-donor-organs
#5
David Juhl, Matthias Marget, Michael Hallensleben, Siegfried Görg, Malte Ziemann
Soon, a virtual crossmatch shall replace the complement-dependent cytotoxicity (CDC) allocation crossmatch in the Eurotransplant region. To prevent positive CDC-crossmatches in the recipient centre, careful definition of unacceptable antigens is necessary. For highly sensitized patients, this is difficult by CDC alone. Assignment of all antibodies detected by sensitive assays, however, could prevent organ allocation. To assess the usefulness of the Luminex C1q-assay to prevent positive CDC-crossmatches, all CDC-crossmatches performed prior to deceased kidney transplantation in a 16-month-period were reviewed...
January 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28077654/neutralization-of-diverse-human-cytomegalovirus-strains-conferred-by-antibodies-targets-viral-gh-gl-pul128-131-pentameric-complex
#6
Sha Ha, Fengsheng Li, Matthew C Troutman, Daniel C Freed, Aimin Tang, John W Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C Nickle, Richard R Rustandi, Melissa Hamm, Pete A DePhillips, Ningyan Zhang, Jason S McLellan, Hua Zhu, Stuart P Adler, Michael A McVoy, Zhiqiang An, Tong-Ming Fu
: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex gH/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross neutralize the field strains of HCMV, remains a challenge...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076415/structure-and-recognition-of-a-novel-hiv-1-gp120-gp41-interface-antibody-that-caused-mper-exposure-through-viral-escape
#7
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N Bhiman, Daniel J Sheward, Debra H Elliott, Julie Rouelle, Ashley Smira, M Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R Burton, Mark Connors, Salim S Abdool Karim, John R Mascola, James E Robinson, Andrew B Ward, Carolyn Williamson, Peter D Kwong, Lynn Morris, Penny L Moore
A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28073404/isolation-and-characterization-of-hiv-1-envelope-glycoprotein-specific-b-cell-from-immortalized-human-na%C3%A3-ve-b-cell-library
#8
Zehua Sun, Shiqiang Lu, Zheng Yang, Jingjing Li, Meiyun Zhang
With the recent development of single B cell cloning techniques, an increasing number of HIV-1-specific broadly neutralizing antibodies (bNAbs) have been isolated since 2009. However, knowledge regarding HIV-1-specific B cells in vivo is limited. In this study, an HIV-1-specific B cell line has been established using healthy PBMC donors by the highly efficient EBV transformation method to generate immortalized human naïve B cell libraries. The enrichment of HIV-1 envelope-specific B cells was observed after four rounds of cell panning with the HIV-1 envelope glycoprotein...
January 10, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28066999/transplant-infectious-diseases-a-review-of-the-scientific-registry-of-transplant-recipients-published-data
#9
Camille N Kotton, Shirish Huprikar, Deepali Kumar
The Scientific Registry of Transplant Recipients (SRTR) serves to collect data on organ transplants done in the United States. Although the infectious diseases data are limited and include mostly pretransplant serologies and other non-specific infection related outcomes, such multicenter data collection allows for insightful national data and the ability to monitor trends over time. We reviewed the published concise reports for each organ type in SRTR reports containing data from 2005-2014, and summarized our findings with respect to cytomegalovirus (CMV), Epstein-Barr virus, posttransplant lymphoproliferative disorder (PTLD), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodefiency virus (HIV), general infection, and prophylaxis...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28066900/boosting-of-post-exposure-human-t-and-b-cell-recall-responses-in-vivo-by-burkholderia-pseudomallei-related-proteins
#10
Arnone Nithichanon, Louise J Gourlay, Gregory J Bancroft, Manabu Ato, Yoshimasa Takahashi, Ganjana Lertmemongkolchai
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with high incidence and mortality in South East Asia and Northern Australia. To date there is no protective vaccine and antibiotic treatment is prolonged and not always effective. Most people living in endemic areas have been exposed to the bacteria and have developed some immunity, which may have helped prevent disease. Here, we used a humanized mouse model (hu-PBL-SCID), reconstituted with human peripheral blood mononuclear cells (PBMCs) from seropositive donors, to illustrate the potential of three known antigens (FliC, OmpA and N-PilO2) for boosting both T- and B-cell immune responses...
January 9, 2017: Immunology
https://www.readbyqxmd.com/read/28061513/angiopoietin-2-blockade-promotes-survival-of-corneal-transplants
#11
Liwei Zhang, Guangyu Li, Roberto Sessa, Gyeong Jin Kang, Meng Shi, Shaokui Ge, Anna Jiang Gong, Ying Wen, Sudhakar Chintharlapalli, Lu Chen
Purpose: Corneal transplantation remains the last hope for vision restoration, and lymphangiogenesis (LG) is a primary mediator of transplant rejection. This study was to investigate the specific role of angiopoietin-2 (Ang-2) in transplantation-associated LG and graft rejection. Methods: Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice to assess the effects of Ang-2 blockade via neutralizing antibody...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#12
Rachel Hogen, Joseph DiNorcia, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress...
January 3, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28058223/acute-antibody-mediated-rejection-after-intestinal-transplantation
#13
Guo-Sheng Wu, Ruy J Cruz, Jun-Chao Cai
AIM: To investigate the incidence, risk factors and clinical outcomes of acute antibody-mediated rejection (ABMR) after intestinal transplantation (ITx). METHODS: A retrospective single-center analysis was performed to identify cases of acute ABMR after ITx, based on the presence of donor-specific antibody (DSA), acute tissue damage, C4d deposition, and allograft dysfunction. RESULTS: Acute ABMR was identified in 18 (10.3%) out of 175 intestinal allografts with an average occurrence of 10 d (range, 4-162) after ITx...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28058219/impact-of-preformed-donor-specific-antibodies-against-hla-class-i-on-kidney-graft-outcomes-comparative-analysis-of-exclusively-anti-cw-vs-anti-a-and-or-b-antibodies
#14
Sofia Santos, Jorge Malheiro, Sandra Tafulo, Leonídio Dias, Rute Carmo, Susana Sampaio, Marta Costa, Andreia Campos, Sofia Pedroso, Manuela Almeida, La Salete Martins, Castro Henriques, António Cabrita
AIM: To analyze the clinical impact of preformed antiHLA-Cw vs antiHLA-A and/or -B donor-specific antibodies (DSA) in kidney transplantation. METHODS: Retrospective study, comparing 12 patients transplanted with DSA exclusively antiHLA-Cw with 23 patients with preformed DSA antiHLA-A and/or B. RESULTS: One year after transplantation there were no differences in terms of acute rejection between the two groups (3 and 6 cases, respectively in the DSA-Cw and the DSA-A-B groups; P = 1)...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28052137/mapping-polyclonal-hiv-1-antibody-responses-via-next-generation-neutralization-fingerprinting
#15
Nicole A Doria-Rose, Han R Altae-Tran, Ryan S Roark, Stephen D Schmidt, Matthew S Sutton, Mark K Louder, Gwo-Yu Chuang, Robert T Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S Abdool Karim, James M Binley, Mark Connors, Barton F Haynes, Malcolm A Martin, David C Montefiori, Lynn Morris, Julie Overbaugh, Peter D Kwong, John R Mascola, Ivelin S Georgiev
Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28029744/high-titer-rheumatoid-arthritis-antibodies-preferentially-bind-fibrinogen-citrullinated-by-peptidyl-arginine-deiminase-4
#16
Nathalie E Blachère, Salina Parveen, Mayu O Frank, Brian D Dill, Henrik Molina, Dana E Orange
OBJECTIVE: Most patients with rheumatoid arthritis (RA) harbor antibodies to citrullinated autoantigens, such as citrullinated fibrinogen. Two isoforms of peptidyl arginine deiminase (PAD), PAD2 and PAD4, which catalyze citrullination with different substrate specificities, can be detected in RA synovium. This study was undertaken to determine whether RA patient antibodies preferentially bind PAD2 or PAD4 citrullinated fibrinogen. METHODS: RA patient and normal donor plasma was tested for binding to PAD2 or PAD4 citrullinated fibrinogen, native fibrinogen, or citrullinated fibrinogen peptides in various dilutions by ELISA and Western blot...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28029430/reduced-human-transitional-b-cell-t1-t2-ratio-is%C3%A2-associated-with-subsequent-deterioration-in%C3%A2-renal-allograft-function
#17
Aravind Cherukuri, Alan D Salama, Clive R Carter, Douglas Landsittel, Gururaj Arumugakani, Brendan Clark, David M Rothstein, Richard J Baker
Human transitional B cells express relatively high IL-10 and low TNF-α levels, which correlate with B regulatory activity in vitro. Herein, we aim to further define B regulatory phenotype and determine whether B regulatory activity can serve as a prognostic marker for renal allograft dysfunction (graft loss or 2-fold fall in estimated glomerular filtration rate). Transitional B cells can be divided into T1 and T2 subsets based on surface phenotype. T1 cells express a significantly higher ratio of IL-10 to TNF-α than T2 cells or other B subsets...
October 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28027625/early-conversion-from-calcineurin-inhibitor-to-everolimus-based-therapy-following-kidney-transplantation-results-of-the-randomized-elevate-trial
#18
Johan W de Fijter, Hallvard Holdaas, Ole Øyen, Jan-Stephan Sanders, Sankaran Sundar, Frederike J Bemelman, Claudia Sommerer, Julio Pascual, Yingyos Avihingsanon, Cholatip Pongskul, Frederic Oppenheimer, Lorenzo Toselli, Graeme Russ, Zailong Wang, Patricia Lopez, Jossy Kochuparampil, Josep M Cruzado, Markus van der Giet
In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated GFR from randomization to month 12, was similar for everolimus versus CNI: mean (SE) 0.3(1.5)mL/min/1.73(2) versus -1.5(1.5)mL/min/1.73(2) (p=0.116). At month 24, mean (SD) estimated GFR was 62...
December 27, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28025936/current-status-of-leukemia-cytotherapy-exploitation-with-immune-cells
#19
Haiyan Bao, Depei Wu
With the development of chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of leukemia patients has been improved greatly in the past few decades. However, relapsed and refractory leukemia is still the major cause of mortality in leukemia patients. Besides, advancing age, poor performance status and severe co-morbidities limit the applicability of cytotoxic chemotherapy in certain groups of leukemia patients. Novel agents including nucleoside analogues, kinase inhibitors targeting oncoproteins and monoclonal antibodies are under investigation for the management of leukemia...
December 26, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28025393/peroxiredoxins-prevent-oxidative-stress-during-human-sperm-capacitation
#20
Donghyun Lee, Adel R Moawad, Tania Morielli, Maria C Fernandez, Cristian O'Flaherty
STUDY QUESTION: Do peroxiredoxins (PRDXs) control reactive oxygen species (ROS) levels during human sperm capacitation? SUMMARY ANSWER: PRDXs are necessary to control the levels of ROS generated during capacitation allowing spermatozoa to achieve fertilizing ability. WHAT IS KNOWN ALREADY: Sperm capacitation is an oxidative event that requires low and controlled amounts of ROS to trigger phosphorylation events. PRDXs are antioxidant enzymes that not only act as scavengers but also control ROS action in somatic cells...
December 26, 2016: Molecular Human Reproduction
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