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allo antibodies

Jian-Ming Li, Christopher T Petersen, Jingxia Li, Reema Panjwani, Daniel J Chandra, Cynthia R Giver, Bruce R Blazar, Edmund K Waller
The goal of allogeneic bone marrow transplantation (allo-BMT) is elimination of leukemia cells through the graft-versus-leukemia (GvL) activity of donor cells, while limiting graft-versus-host disease (GvHD). Immune checkpoint pathways regulate GvL and GvHD activities, but blocking antibodies or genetic inactivation of these pathways can cause lethal GVHD. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide that regulates co-inhibitory pathways; its role in allo-BMT has not been studied...
September 26, 2016: Cancer Research
Gheath Alatrash, Naval Daver, Elizabeth A Mittendorf
The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies...
October 2016: Pharmacological Reviews
Sean D Owens, Amir Kol, Naomi J Walker, Dori L Borjesson
Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs...
2016: Stem Cells International
Anna Buermann, Dorothee Römermann, Wiebke Baars, Joachim Hundrieser, Jürgen Klempnauer, Reinhard Schwinzer
BACKGROUND: The development of donor-reactive antibodies is regarded to be an important barrier limiting long-term outcome of allo- and xenografts. We asked whether enhanced signaling via the co-inhibitory receptor programmed cell death-1 (PD-1; CD279) can downregulate human B-cell activation. METHODS: Proliferation of human purified CD19(+) B cells was induced by in vitro stimulation with CpG oligodeoxynucleotides (CpG-B). To induce antibody production, peripheral blood mononuclear cells were co-cultured with the porcine B-cell line L23...
September 2016: Xenotransplantation
Ashish Jain, Ajju Agnihotri, Neelam Marwaha, Ratti Ram Sharma
INTRODUCTION: Red cell allo- and auto-immunization is a well recognized problem in multi-transfused thalassemic patients. We conducted this study on 301 multi-transfused thalassemic patients under the Thalassemia Transfusion Programme of Advanced Pediatric Centre of PGIMER. AIMS AND OBJECTIVES: The study was designed to determine the frequency of alloimmunization and autoimmunization in multi-transfused thalassemic patients and to establish the specificity of alloantibody to red cell antigens, if alloimmunization is detected...
July 2016: Asian Journal of Transfusion Science
R Petermann
Neonatal immune thrombocytopenia represent less than 5% of cases of early thrombocytopenia (early-onset<72hours post-delivery). As in adults, thrombocytopenia in neonates is defined as a platelet count less than 150G/L. They are either auto- or allo-immune. Thrombocytopenia resulting from transplacental passage of maternal antibodies directed to platelet membrane glycoproteins can be severe. The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial haemorrhage and neurologic sequelea following...
August 31, 2016: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Irina A Isakova, Kate C Baker, Jason Dufour, Donald G Phinney
: : Krabbe disease, or globoid cell leukodystrophy, is a rare disorder caused by deficient galactosylceramidase activity and loss of myelin-forming oligodendrocytes, resulting in progressive demyelination and severely impaired motor function. Disease symptoms in humans appear within 3-6 months of age (early infantile) and manifest as marked irritability, spasticity, and seizures. The disease is often fatal by the second year of life, with few effective treatment options. Herein we evaluated the therapeutic potential of mesenchymal stem cells (MSCs) administered intracranially to a 1-month-old rhesus macaque diagnosed with severe early-onset Krabbe disease that displayed neurologic and behavioral symptoms similar to those of human patients...
August 24, 2016: Stem Cells Translational Medicine
Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT...
October 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Undine A Gerlach, Nils Lachmann, Giuseppina Ranucci, Birgit Sawitzki, Constanze Schoenemann, Johann Pratschke, Duska Dragun, Andreas Pascher
BACKGROUND: Non-HLA-allo- and autoantibodies are involved in allograft rejection in kidney and heart transplantation. Their role in intestinal transplantation has not yet been described. We examined the development of anti-Angiotensin II type I receptor antibodies (anti-AT1R) and anti-Endothelin-Type A receptor antibodies (anti-ETAR) associated with the clinical course and histopathological findings of ITX-recipients. METHODS: 37 patients underwent intestinal or multivisceral transplantation...
August 5, 2016: Transplantation
Malvezzi Paolo, Jouve Thomas, Rostaing Lionel
In the setting of solid-organ transplantation, calcineurin inhibitor (CNI)-based therapy remains the cornerstone of immunosuppression. However, long-term use of CNIsis associated with some degree of nephrotoxicity. This has led to exploring the blockadeof some costimulation pathways as an efficient immunosuppressive tool instead of using CNIs. The only agent already in clinical use and approved by the health authorities for kidney-transplant patients is belatacept (Nulojix): a fusion protein that interferes with CTLA-4...
July 28, 2016: Transplantation
Ann R Kennedy, Amit Maity, Jenine K Sanzari
Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation...
August 2016: Radiation Research
Laura A Michielsen, Arjan D van Zuilen, Merle M Krebber, Marianne C Verhaar, Henny G Otten
HLA antibodies play a major role in the recipient's immune response against the renal allograft and are an established risk factor for antibody-mediated rejection and subsequent impaired graft survival. Evidence originating from HLA-identical donor-recipient pairs indicates that non-HLA antibodies may play a role as well. Numerous non-HLA antibodies have been identified in renal organ transplantation, directed against a heterogeneous subset of both allo- and autoantigens including MHC Class-I-related chain A (MICA) and Angiotensin II type 1 receptor (AT1R)...
October 2016: Transplantation Reviews
Agnes M Azimzadeh, Tianshu Zhang, Guosheng Wu, Shahrooz S Kelishadi, Tiffany Stoddard, Natalie OʼNeill, Bao-Ngoc Nguyen, Emily Welty, Christopher Avon, Mitch Higuchi, Stuart L Mitchell, Alena Hershfeld, Xiang-Fei Cheng, Anthony Kronfli, Elana Rybak, Lars Burdorf, Richard N Pierson
BACKGROUND: Anti-CD154 monotherapy is associated with antidonor allo-antibody (Ab) elaboration, cardiac allograft vasculopathy (CAV), and allograft failure in preclinical primate cell and organ transplant models. In the context of calcineurin inhibitors (CNI), these pathogenic phenomena are delayed by preemptive "induction" B cell depletion. METHODS: αCD154 (IDEC-131)-treated cynomolgus monkey heart allograft recipients were given peritransplant rituximab (αCD20) alone or with rabbit antihuman thymocyte globulin...
June 29, 2016: Transplantation
Yanan Guo, Xiaoli Feng, Yang Jiang, Xiaoyun Shi, Xiangling Xing, Xiaoli Liu, Nailin Li, Bengt Fadeel, Chengyun Zheng
Aiming for an adoptive natural killer (NK) cell therapy, we have developed a novel protocol to expand NK cells from peripheral blood. With this protocol using anti-human CD16 antibody and interleukin (IL)-2, NK (CD3-CD56+) cells could be expanded about 4000-fold with over 70% purity during a 21-day culture. The expanded NK (exNK) cells were shown to be highly cytotoxic to multiple myeloma (MM) cells (RPMI8226) at low NK-target cell ratios. Furthermore, NK cells expanded in the presence of a blocking antibody (exNK+PD1-blockage) against programmed cell death protein-1 (PD1), a key counteracting molecule for NK and T cell activity, demonstrated more potent cytolytic activity against the RPMI8226 than the exNK cells without PD1 blocking...
June 23, 2016: Oncotarget
George W Burke, Linda J Chen, Gaetano Ciancio, Alberto Pugliese
PURPOSE OF REVIEW: The review analyzes the current biomarkers used in monitoring pancreas transplant, from the simple and time-tested, to more sophisticated, including markers of allo- and autoimmunity, that are likely to play a larger role in future studies. RECENT FINDINGS: Evaluation of alloimmunity includes serum levels of donor-specific antibody, and, ultimately, pancreas transplant biopsies with C4d staining. Our center has focused on markers of autoimmunity, including assessment of autoantibodies and autoreactive T cells...
August 2016: Current Opinion in Organ Transplantation
Ross M Fasano, Stella T Chou
Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required...
October 2016: Transfusion Medicine Reviews
Yue-Hua Huang, Wei Zhang, Hao Cai, Tian-Jiao Li, Jian Li, Bing Han, Jun-Ling Zhuang, Tie-Nan Zhu, Hua-Cong Cai, Dao-Bin Zhou
BACKGROUND: CD200 and its receptor CD200R are both type-1 membrane glycoproteins, which are members of the immunoglobulin superfamily (IgSF). Besides the inhibitory effect on macrophages, CD200/CD200R also play an important role in regulating the regulatory T cells, allergicreaction, autoimmune diseases, allograft, neurological diseases and other autoimmune-related diseases, etc. OBJECTIVE: To investigate the role of CD200 and its receptor in the graft versus host disease (GVHD)...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
S Varma, J Ambroise, M Komuta, D Latinne, P Baldin, R Reding, F Smets, X Stephenne, E M Sokal
AIM: To determine predisposing factors of idiopathic allograft fibrosis among pediatric liver transplant recipients. BACKGROUND: Protocol biopsies (PB) from stable liver transplant (LT) recipient children frequently exhibit idiopathic fibrosis. The relation between allograft inflammation, humoral immune response and fibrosis is uncertain. Also the role of HLA-DRB1 genotype has not been evaluated, though it's associated with fibrosis in autoimmune hepatitis. PATIENTS AND METHODS: This observational study, included 89 stable LT recipient transplanted between 2004-2012 with mean follow-up of 4...
July 2016: EBioMedicine
A M Brunner, A T Fathi, Y B Chen
Allogeneic hematopoietic cell transplantation (allo-HCT) for patients with AML is increasingly able to impact the historically poor outcomes in this disease. Nonetheless, even with transplant, the rates of post-HCT relapse are unacceptably high, and remain a great challenge in the treatment of patients with AML. Maintenance therapies after allo-HCT, given to patients at high risk of relapse or with evidence of minimal residual disease (MRD), may provide a way to reduce relapse rates and improve survival. New therapies may offer acceptable toxicity profiles in the post-HCT setting, and investigations are ongoing using hypomethylating agents, histone deacetylase inhibitors, immunomodulatory drugs, targeted tyrosine kinase inhibitors, drug-antibody conjugates and cellular therapies...
June 20, 2016: Bone Marrow Transplantation
Sandy Feng, Anthony J Demetris, Katharine M Spain, Sai Kanaparthi, Bryna E Burrell, Udeme D Ekong, Estella M Alonso, Philip Rosenthal, Laurence A Turka, David Ikle, Nadia K Tchao
: Pediatric liver transplant recipients arguably have the most to gain and the most to lose from discontinuing immunosuppression (IS). While IS undoubtedly exerts a cumulative toll, there is concern that insufficient or no IS may contribute to allograft deterioration. Twelve pediatric recipients of parental living donor liver grafts, identified as operationally tolerant through complete IS withdrawal (WISP-R; NCT00320606) were followed for a total of five years (one year of IS withdrawal and four years off IS) with serial liver tests, auto- and allo-antibody assessments...
June 15, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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