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allo antibodies

Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P Flynn, David Bastian, M Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R Blazar, Xue-Zhong Yu
Chronic graft-versus-host disease (cGVHD) is characterized as autoimmune-like fibrosis and antibody production mediated by pathogenic T-cells and B-cells. MicroRNA (miR)-17-92 influences the survival, differentiation and function of lymphocytes in cancer, infections and autoimmunity. To determine whether miR-17-92 regulates T- and B-cell responses in cGVHD, we generated mice conditionally deficient for miR-17-92 in T-cells, B-cells, or both. Using murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that expression of miR-17-92 in donor T- and B-cells is essential for the induction of both scleroderma and bronchiolitis obliterans in cGVHD...
March 12, 2018: Blood
Dalia M El Dewi, Tarek Metwally
Warm auto-antibodies are directed against patients' own red blood cell antigens and can interfere with and complicate investigations for the detection and identification of RBC allo-antibodies. Most patients with autoimmune hemolytic anemia (AIHA) have already been transfused and the patients' phenotype can be difficult to determine. In warm type AIHA; the auto- antibodies in the patient's serum react with all normal red blood cells and make it impossible to find compatible blood. Special appropriate compatibility test procedures in a reference laboratory allow the detection and identification of clinically significant allo- Abs that may be masked by the auto- Abs...
June 2017: Egyptian Journal of Immunology
Moniek A de Witte, Dhifaf Sarhan, Zachary Davis, Martin Felices, Daniel A Vallera, Peter Hinderlie, Julie Curtsinger, Sarah Cooley, John Wagner, Jurgen Kuball, Jeffrey S Miller
Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HCT). NK cells and γδ T cells reconstitute early after allo-HCT, contribute to tumor immunosurveillance via MHC independent mechanisms and do not induce graft-versus-host disease (GVHD). Here we performed a quantitative and qualitative analysis of the NK and γδ T cell repertoire in healthy individuals, recipients of HLA-matched sibling or unrelated donor allo-HCT (MSD/MUD-HCT) and umbilical cord blood-HCT (UCB-HCT)...
March 2, 2018: Biology of Blood and Marrow Transplantation
Senthilkumar Alagesan, Clara Sanz-Nogués, Xizhe Chen, Michael Creane, Thomas Ritter, Rhodri Ceredig, Timothy O'Brien, Matthew D Griffin
Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf" therapy with anti-inflammatory and pro-repair properties. This study investigated humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were determined in sera from healthy mice two weeks after single or repeated IM injections of fully-MHC-mismatched allo-MSC with comparison to mice receiving syngeneic MSC, allogeneic splenocytes or saline...
February 15, 2018: Immunology and Cell Biology
Bhagirathbhai R Dholaria, Ernesto Ayala, Lubomir Sokol, Taiga Nishihori, Julio C Chavez, Mohammad Hussaini, Ambuj Kumar, Mohamed A Kharfan-Dabaja
BACKGROUND: T- cell prolymphocytic leukemia (T- PLL) is a rare aggressive hematological malignancy. Alemtuzumab, an anti-CD52 humanized monoclonal antibody, is the treatment of choice for remission induction. Allogeneic hematopoietic cell transplantation (allo-HCT) has been described to induce durable remissions and improve survival, but data is limited. PATIENTS AND METHODS: We evaluated clinical outcomes of 11 patients, median age of 56 (range, 43-71) years who underwent allo-HCT for T-PLL...
January 29, 2018: Leukemia Research
Michael G Fitzsimons, Rebecca Karp Leaf, Johnathan Mack, Pavan K Bendapudi, Tao Shen, Duke E Cameron
Factor XI deficiency is associated with significant bleeding in the setting of trauma and surgery. We present a patient with FXI deficiency and multiple red blood cell allo-antibodies requiring repeat aortic root replacement and discuss the perioperative management of patients with FXI deficiency undergoing cardiac surgery.
February 4, 2018: Journal of Cardiac Surgery
Moniek A de Witte, Jürgen Kuball, Jeffrey S Miller
Purpose of review: The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors which both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing Graft-versus-Host Disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis...
December 2017: Current Stem Cell Reports
Qi Hao, Shu-Qin Zhang, Dong-Mei Zhang, Jing-Bo Wang, Jie Zhao, Hao-Yu Cheng
OBJECTIVE: To investigate the value of flow cytometry (FCM) detection in prognostic evaluation of minimal residual disease (MRD) of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Eighty-two cases of AML (except M3) after allo-HSCT who accord to enrolled condition (no MRD positive after allo-HSCT confirmed by regular flow cytometry detection and followed-up for 2 years) from April 2012 to September 2016 in our department were selected...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jing Du, Ryan Flynn, Katelyn Paz, Hong-Gang Ren, Yuko Ogata, Qing Zhang, Philip R Gafken, Barry E Storer, Nathan H Roy, Janis K Burkhardt, Wendy Mathews, Jakub Tolar, Stephanie J Lee, Bruce R Blazar, Sophie Paczesny
Improved diagnostic and treatment methods are needed for chronic graft-versus-host disease (cGVHD), the leading cause of late non-relapse mortality (NRM) in long-term survivors of allogenic hematopoietic cell transplantation (allo-HCT). Validated biomarkers that facilitate disease diagnosis, and classification generally are lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well-established murine multi-organ system cGVHD model. We discovered 4 up-regulated proteins during cGVHD that are targetable by genetic ablation or blocking antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8 and CCL9 chemokines...
January 18, 2018: Blood
Kitty de Leur, Marian C Clahsen-van Groningen, Thierry P P van den Bosch, Gretchen N de Graav, Dennis A Hesselink, Janneke N Samsom, Carla C Baan, Karin Boer
BACKGROUND: We hypothesize that T cells such as IL-21+BCL6+ T follicular helper cells can regulate B cell mediated immunity within the allograft during acute T-cell mediated rejection, this process may feed chronic allograft rejection on long term. To investigate this mechanism we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. METHODS: Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI), and acute T cell-mediated rejection grade II (aTCMRII)...
January 10, 2018: Clinical and Experimental Immunology
Baixin Ye, Daniel Smerin, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
The diagnostic, monitoring and therapeutic options for cancers currently remain limited. These limitations represent a large threat to human health. Adaptive immunity, which is dependent on diverse repertoires of B cell receptors (BCRs) and T cell receptors (TCRs), plays a critical role in the anti-tumor immune response. Modulation and surveillance of adaptive immunity has become a powerful weapon to combat cancers. Recently, the high-throughput sequencing of immune repertoire (HTS-IR) technology, which provides a robust tool for deep sequencing repertoires of BCRs or TCRs, has been applied in the development of tumor biomarkers and immunotherapeutics for cancers...
March 1, 2018: Cancer Letters
María José Martínez-Bravo, Berta Sánchez, María José Acevedo, José Antonio Pérez-Simón, Antonio Núñez-Roldán, Isabel Aguilera
Donor-specific antibodies against Glutathione S-transferase T1 (GSTT1) have been associated with de novo immune hepatitis after liver transplantation. These antibodies have also been found very early in allo-HCT associated with acute hepatic GvHD but in all the cases the donor cells had experienced previous priming through pregnancies. It remained to be explored whether or not primary recognition of the antigen occurs after HCT and what could be the consequences in the long term outcome. We genotyped a cohort of 68 HCT patients and found 11 with the GSTT1 null donor/positive recipient mismatch...
December 13, 2017: Transplant Immunology
Tim J A Hutten, Wieger J Norde, Rob Woestenenk, Ruo Chen Wang, Frans Maas, Michel Kester, J H Frederik Falkenburg, Sofia Berglund, Leo Luznik, Joop H Jansen, Nicolaas Schaap, Harry Dolstra, Willemijn Hobo
Allogeneic stem cell transplantation (allo-SCT) can be a curative treatment for patients with a hematologic malignancy due to alloreactive T cell responses recognizing minor histocompatibility antigens (MiHA). Yet tumor immune escape mechanisms can cause failure of T cell immunity, leading to relapse. Tumor cells display low expression of costimulatory molecules and can up-regulate coinhibitory molecules that inhibit T cell functionality on ligation with their counter-receptors on the tumor-reactive T cells...
December 26, 2017: Biology of Blood and Marrow Transplantation
Anastasia Mavropoulos, Bedilu Allo, Mingxiao He, Emily Park, Daniel Majonis, Olga Ornatsky
Mass cytometry uniquely enables high-dimensional single-cell analysis of complex populations. This recently developed technology is based on inductively coupled time-of-flight mass spectrometry for multiplex proteomic analysis of more than 40 markers per cell. The ability to characterize the transcriptome is critical for the understanding of disease pathophysiology, medical diagnostics, and drug discovery. Current techniques allowing the in situ detection of transcripts in single cells are limited to a small number of simultaneous targets and are generally tedious and labor-intensive...
December 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
K P Samy, R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the poorly understood instant blood-mediated inflammatory reaction and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses with alloislet (AI) responses in primates. We recently developed a dual islet transplant model, which enables direct histologic comparison of early engraftment immunobiology...
November 25, 2017: American Journal of Transplantation
Basile Nsimba
L'éditeur a le regret de vous informer que cet article a déjà été publié dans: Journal of Blood Disorders & Transfusion, 2017, 8:4. DOI: 10.4172/2155-9864.1000388. Cette seconde publication faite par erreur a été retirée.
November 22, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
Heleen van den Heuvel, Kirstin M Heutinck, Ellen M W van der Meer-Prins, Marry E I Franke-van Dijk, Paula P M C van Miert, Xiaoqian Zhang, Ineke J M Ten Berge, Frans H J Claas
Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through cross-reactivity of their T-cell receptor (TCR). In a transplantation setting, such allo-HLA cross-reactivity may contribute to harmful immune responses towards the allograft, provided that the cross-reactive T cells get sufficiently activated upon recognition of the allo-HLA. An important determinant of T-cell activation is TCR avidity, which to date, has remained largely unexplored for allo-HLA-cross-reactive virus-specific T cells. For this purpose, cold target inhibition assays were performed using allo-HLA-cross-reactive virus-specific memory CD8(+) T-cell clones as responders, and syngeneic cells loaded with viral peptide and allogeneic cells as hot (radioactively-labeled) and cold (non-radioactively-labeled) targets...
October 31, 2017: Human Immunology
Myo Htut, Anita D'Souza, Amrita Krishnan, Benedetto Bruno, Mei-Jie Zhang, Mingwei Fei, Miguel Angel Diaz, Edward Copelan, Siddhartha Ganguly, Mehdi Hamadani, Mohamed Kharfan-Dabaja, Hillard Lazarus, Cindy Lee, Kenneth Meehan, Taiga Nishihori, Ayman Saad, Sachiko Seo, Muthalagu Ramanathan, Saad Z Usmani, Christina Gasparetto, Tomer M Mark, Yago Nieto, Parameswaran Hari
We compared postrelapse overall survival (OS) after autologous/allogeneic (auto/allo) versus tandem autologous (auto/auto) hematopoietic cell transplantation (HCT) in patients with multiple myeloma (MM). Postrelapse survival of patients receiving an auto/auto or auto/allo HCT for MM and prospectively reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2010 were analyzed. Relapse occurred in 404 patients (72.4%) in the auto/auto group and in 178 patients (67.4%) in the auto/allo group after a median follow-up of 8...
March 2018: Biology of Blood and Marrow Transplantation
Emma Fosbury, Anja Drebes, Anne Riddell, Pratima Chowdary
Acquired haemophilia A (AHA) is a rare, serious bleeding disorder most often encountered in elderly patients. The mainstay of haemostatic management is with bypassing agents (BPAs) including recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCCs). Their major limitation is incomplete efficacy, potential risk for thrombosis and the lack of routine laboratory assays for monitoring treatment response. Plasma-derived porcine FVIII (pd-pFVIII, Hyate C(®)), first used in the 1950s for the management of congenital haemophilia, has sufficient sequence homology to be haemostatic in humans, but the lack of complete homology facilitates efficacy even in the presence of human allo- and autoantibodies against human FVIII (hFVIII)...
September 2017: Therapeutic Advances in Hematology
Barbara Dillinger, Sarah Ahmadi-Erber, Klara Soukup, Angela Halfmann, Silke Schrom, Bernard Vanhove, Peter Steinberger, Rene Geyeregger, Stephan Ladisch, Alexander Michael Dohnal
Donor T-cells contribute to reconstitution of protective immunity after allogeneic hematopoietic stem cell transplantation (HSCT) but must acquire specific tolerance against recipient alloantigens to avoid life-threatening graft-versus-host disease (GvHD). Systemic immunosuppressive drugs may abrogate severe GvHD, but this also impedes memory responses to invading pathogens. Here, we tested whether ex vivo blockade of CD28 co-stimulation can enable selective T-cell tolerization to alloantigens by facilitating CD80/86-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling...
2017: Frontiers in Immunology
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