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Alloimmunity

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https://www.readbyqxmd.com/read/28340248/irradiation-of-red-blood-cells-and-alloimmunization
#1
Christopher A Tormey, Jeanne E Hendrickson
Background: Animal models suggest that red blood cell (RBC) damage incurred during storage can increase immunogenicity to some RBC antigens. We hypothesized that RBC irradiation, a source of oxidative damage, may result in higher RBC alloimmunization rates among transfusion recipients. Methods: Individuals receiving 1 or more gamma-irradiated RBC units, with follow-up antibody screening, were studied. We recorded diagnosis at the time of first irradiated RBC-unit transfusion, total irradiated RBCs received, and alloantibodies detected before and after irradiated RBC transfusion...
March 18, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28337751/a-novel-network-analysis-tool-to-identify-relationships-between-disease-states-and-risks-for-red-blood-cell-alloimmunization
#2
R Celli, W Schulz, J E Hendrickson, C A Tormey
We hypothesized that diagnoses may be associated with alloantibody 'responder' status and examined associations between disease states and alloimmunization. Patients with ≥1 alloantibody and non-alloimmunized controls were analysed. Pearson's coefficients were calculated to determine associations between alloimmunization and diseases; significant correlations were selected to construct a network. Inflammatory disorders and diseases requiring chronic transfusion support were associated with responder status...
March 23, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#3
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#4
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318185/neonatal-acute-liver-failure-a-diagnosis-challenge
#5
Mirta Ciocca, Fernando Álvarez
Neonatal acute liver failure is a rare, very severe disease with a high rate of mortality. It is clinically and etiologically different from acute liver failure seen in older children and adults. Coagulopathy with an international normalized ratio ≥ 3 is the critical parameter that defines it. The most common causes are fetal alloimmune hepatitis, previously called neonatal hemochromatosis, viral infections, metabolic disorders, and hemophagocytic lymphohistiocytosis. There is a group of treatable diseases that require a very early diagnosis for the prescription of an adequate treatment...
April 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28316442/alloimmunization-in-autoimmune-hemolytic-anemia-patient-the-differential-adsorption-approach
#6
Ravi C Dara, Aseem Kumar Tiwari, Dinesh Arora, Subhasis Mitra, Devi Prasad Acharya, Geet Aggarwal, Jyoti Sharma
Patients of β-thalassemia major are dependent on regular blood transfusions for their entire lifetime. Development of antibodies against red blood cell (RBC) antigen which may be alloantibody or autoantibody, several times as a result of frequent red cell component transfusions, further complicates the subsequent transfusion therapy. Among the autoantibodies, warm-reactive autoantibodies are commoner and interfere in the pretransfusion testing. These RBC autoantibodies present in patient's serum potentially react with all the cells of antibody identification panel giving "pan-reactive" picture and making alloantibody identification complex...
January 2017: Asian Journal of Transfusion Science
https://www.readbyqxmd.com/read/28300768/tim-3-as-a-target-for-cancer-immunotherapy-and-mechanisms-of-action
#7
REVIEW
Wenwen Du, Min Yang, Abbey Turner, Chunling Xu, Robert L Ferris, Jianan Huang, Lawrence P Kane, Binfeng Lu
Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28299024/plasma-neutrophil-gelatinase-associated-lipocalin-as-a-marker-for-prediction-of-3-month-graft-survival-after-kidney-transplantation
#8
A Jafari, M R Khatami, S Dashti-Khavidaki, M Lessan-Pezeshki, A Abdollahi
BACKGROUND: Ischemic injury during organ transplantation increases the risk of acute and chronic rejections by promoting alloimmune responses. Measurement of neutrophil gelatinase-associated lipocalin (NGAL) immediately after kidney transplantation may be promising for early detection of ischemic injuries to allograft. OBJECTIVE: This study assessed possible predictive values of plasma NGAL levels during first hours after kidney transplantation for graft loss within the first 3 months after transplantation...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-il6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#9
Zhabiz Solhjou, Mayuko Uehara, Baharak Bahmani, Omar H Maarouf, Takaharu Ichimura, Craig R Brooks, Wanlong Xu, Mine Yilmaz, Abdala Elkhal, Stefan G Tullius, Indira Guleria, Martina McGrath, Reza Abdi
Ischemia reperfusion injury (IRI) evokes intra-graft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DC). While autophagy is a survival mechanism for ischemic DC, it also augments their production of IL6. Allograft derived dendritic cells (ADDC) lacking autophagy related gene 5 (Atg5) showed higher death rates post-transplantation...
March 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28295360/human-platelet-antigen-antibody-induction-in-uncomplicated-pregnancy-is-associated-with-hla-sensitization
#10
Viktoria S A Reiher, Gideon Hönger, Laura Infanti, Jakob R Passweg, Irene Hösli, Beat M Frey, Christoph Gassner, Stefan Meyer, Andreas S Buser, Andreas Holbro, Stefan Schaub
BACKGROUND: Alloimmunization against human platelet antigens (HPAs) during pregnancy is rare but can lead to severe bleeding disorders, such as fetal and neonatal alloimmune thrombocytopenia. STUDY DESIGN AND METHODS: In a cohort of 241 uncomplicated pregnancies, we investigated the immunogenicity of HPA mismatches and correlated HLA sensitization with HPA antibody formation. HPA antibodies were measured with a Luminex-based multiplex assay. RESULTS: HPA mismatches were observed in 109 of 241 pregnancies (45%), but child-specific HPA antibodies were only found in two of 109 cases (2%), indicating a low immunogenicity...
March 10, 2017: Transfusion
https://www.readbyqxmd.com/read/28295352/should-optimal-timing-between-two-intrauterine-transfusions-be-based-on-estimated-daily-decrease-of-hemoglobin-or-on-measurement-of-fetal-middle-cerebral-artery-peak-systolic-velocity
#11
Louise Ghesquière, Véronique Houfflin-Debarge, Hélène Behal, Capucine Coulon, Damien Subtil, Pascal Vaast, Charles Garabedian
BACKGROUND: To best predict the recurrence of fetal anemia after intrauterine transfusion (IUT), the measurement of middle cerebral artery peak systolic velocity (PSV) and the estimation of hemoglobin (Hb) daily decrease are compared. STUDY DESIGN AND METHODS: A retrospective study including 38 patients who had at least two IUTs in a context of red blood cell alloimmunization was conducted. PSV values before first, second, and third IUTs were collected and expected Hb level was calculated according to various Hb daily decrease formulas as proposed in the literature...
March 14, 2017: Transfusion
https://www.readbyqxmd.com/read/28294127/orai2-modulates-store-operated-calcium-entry-and-t-cell-mediated-immunity
#12
Martin Vaeth, Jun Yang, Megumi Yamashita, Isabelle Zee, Miriam Eckstein, Camille Knosp, Ulrike Kaufmann, Peter Karoly Jani, Rodrigo S Lacruz, Veit Flockerzi, Imre Kacskovics, Murali Prakriya, Stefan Feske
Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is critical for lymphocyte function and immune responses. CRAC channels are hexamers of ORAI proteins that form the channel pore, but the contributions of individual ORAI homologues to CRAC channel function are not well understood. Here we show that deletion of Orai1 reduces, whereas deletion of Orai2 increases, SOCE in mouse T cells. These distinct effects are due to the ability of ORAI2 to form heteromeric channels with ORAI1 and to attenuate CRAC channel function...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28293401/alloimmunization-in-patients-with-sickle-cell-disease-and-thalassemia-experience-of-a-single-centre-in-oman
#13
Salam Alkindi, Saba AlMahrooqi, Sumaiya AlHinai, Ali AlMarhoobi, Saif Al-Hosni, Shahina Daar, Naglaa Fawaz, Anil Pathare
BACKGROUND: Blood transfusion is an integral part of the supportive care for patients with sickle cell disease (SCD) and thalassaemia. The hazard of red cell alloimmunization, however, is one of the main complications of this therapy. OBJECTIVES: The aim of this study was to evaluate the prevalence of red cell alloimmunization in Omani patients with sickle cell anaemia and thalassemia. METHODS: This study included 262 patients whose historical transfusion records were available...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28286630/a-fatal-case-of-immune-hyperhemolysis-with-bone-marrow-necrosis-in-a-patient-with-sickle-cell-disease
#14
Matthew S Karafin, Arun Singavi, Susan T Johnson, Joshua J Field
In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis...
February 23, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28278506/accuracy-of-middle-cerebral-artery-doppler-assessment-between-34-and-37-weeks-in-fetuses-with-red-cell-alloimmunization
#15
Emeline Maisonneuve, Aude Jayot, Stéphanie Friszer, Vanina Castaigne, Evelyne Cynober, Françoise Pernot, Agnès Mailloux, Jean-Marie Jouannic, Anne Cortey, Bruno Carbonne
BACKGROUND: The Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) is considered the gold standard for the noninvasive detection of moderate to severe anemia. However, the accuracy of this test has not been evaluated so far, specifically beyond 34 weeks. OBJECTIVES: To assess the accuracy of MCA-PSV to detect moderate to severe fetal anemia and to identify risk factors associated with false-positive and false-negative MCA-PSV values after 34 weeks...
March 10, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28276660/complement-alternative-pathway-deficiency-in-recipients-protects-kidney-allograft-from-ischemia-reperfusion-injury-and-alloreactive-t-cell-response
#16
Federica Casiraghi, Nadia Azzollini, Marta Todeschini, Sonia Fiori, Regiane Aparecida Cavinato, Paola Cassis, Samantha Solini, Francesca Pezzuto, Marilena Mister, Joshua M Thurman, Ariela Benigni, Giuseppe Remuzzi, Marina Noris
Despite the introduction of novel and more targeted immunosuppressive drugs, the long-term survival of kidney transplants has not improved satisfactorily. Early antigen-independent intra-graft inflammation plays a critical role in the initiation of the alloimmune response and impacts long-term graft function. Complement activation is a key player both in ischemia/reperfusion injury (IRI) as well as in adaptive anti-graft immune response after kidney transplantation. Since the alternative pathway (AP) amplifies complement activation regardless of the initiation pathways and renal IR injured cells undergo uncontrolled complement activation, we wondered whether selective blockade of AP could be a strategy for prolonging kidney graft survival...
March 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28275334/clinical-significance-of-an-alloantibody-against-the-kell-blood-group-glycoprotein
#17
Stella Maris Mattaloni, Carine Arnoni, Rosario Céspedes, Claudia Nonaka, Carolina Trucco Boggione, Melina Eliana Luján Brajovich, Andrea Trejo, Néstor Zani, Claudia Silvia Biondi, Lilian Castilho, Carlos Miquel Cotorruelo
BACKGROUND: Kell null (K0) individuals can produce anti-Ku, an antibody against many epitopes in the Kell glycoprotein, after transfusion and/or pregnancy. Since sensitized K0 patients are rare, little is known about anti-Ku clinical relevance and in particular about its association to hemolytic disease of the fetus and newborn. CASE REPORT: This work describes a case of neonatal hyperbilirubinemia due to immune-mediated erythrocyte destruction by an alloantibody directed against the Kell glycoprotein...
January 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28262226/taking-a-wider-view-on-fetal-neonatal-alloimmune-thrombocytopenia
#18
Lilach Bonstein, Nuhad Haddad
In fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelets are destroyed by maternal antibodies directed against fetal/neonate antigens. Thrombocytopenia can be severe and lead to intracranial hemorrhage (ICH) in about 10% of cases. Although three types of antigen groups, presented on platelets [ABO blood group antigens, human leukocyte antigens (HLA) and human platelet antigens (HPA)] are known to be implicated in immune platelet destruction, antibodies against HPA are most commonly involved in FNAIT and hence are the target of extensive research...
March 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28261322/immune-regulation-of-sickle-cell-alloimmunization
#19
Karina Yazdanbakhsh, Beth H Shaz, Christopher D Hillyer
Red blood cell (RBC) transfusion remains an important treatment for patients with sickle cell disease (SCD) and the majority of patients receive transfusions by adulthood. However, SCD patients are at a high risk of alloimmunization, which can cause life-threatening complications. The high rate of alloimmunization can in part be explained by chronic inflammatory condition in SCD characterized by significant immune and inflammatory activation. Heightened immune effector cell responses and/or impaired regulatory networks are likely to drive alloantibody production in alloimmunized SCD patients...
February 2017: ISBT Science Series
https://www.readbyqxmd.com/read/28261211/targeting-the-monocyte-macrophage-lineage-in-solid-organ-transplantation
#20
REVIEW
Thierry P P van den Bosch, Nynke M Kannegieter, Dennis A Hesselink, Carla C Baan, Ajda T Rowshani
There is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair...
2017: Frontiers in Immunology
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