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Alloimmunity

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https://www.readbyqxmd.com/read/28644735/fetal-and-neonatal-alloimmune-thrombocytopenia-evidence-based-antenatal-and-postnatal-management-strategies
#1
Dian Winkelhorst, Dick Oepkes, Enrico Lopriore
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare but potentially lethal disease, leading to severe bleeding complications in 1 in 11.000 newborns. It is the leading cause of thrombocytopenia in healthy term-born neonates. Areas covered: This review summarizes the antenatal as well as postnatal treatment, thus creating a complete overview of all possible management strategies for FNAIT. Expert commentary: The optimal antenatal therapy in order to prevent bleeding complications in pregnancies complicated by FNAIT is non-invasive treatment with weekly intravenous immunoglobulin (IVIG)...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28643663/delivery-outcomes-of-term-pregnancy-complicated-by-idiopathic-polyhydramnios
#2
S Zeino, L Carbillon, I Pharisien, A Tigaizin, M Benchimol, R Murtada, J Boujenah
OBJECTIVE: Polyhydramnios is associated with an increased risk of cesarean section. The aetiology of polyhydramnios and the characteristics of the labour may be confounding factors. The objective was to study the characteristics and mode of delivery in case of pregnancy complicated with idiopathic polyhydramnios. METHODS: This retrospective matched and controlled study included all pregnant women with idiopathic polyhydramnios (amniotic index>25cm or single deepest pocket>8cm) diagnosed at the 2nd or 3rd trimester and persistent at term delivery (>37weeks of pregnancy) in our institution...
April 2017: Journal of gynecology obstetrics and human reproduction
https://www.readbyqxmd.com/read/28643386/risks-and-trends-of-red-blood-cell-transfusion-in-obstetric-patients-a-retrospective-study-of-45-213-deliveries-using-administrative-data
#3
Nadine Shehata, Michaël Chassé, Jo Ann Colas, Malia Murphy, Alan J Forster, Ann K Malinowski, Robin Ducharme, Dean A Fergusson, Alan Tinmouth, Kumanan Wilson
BACKGROUND: Transfusion data for obstetric patients are scarce. Identifying characteristics associated with red blood cell transfusion (RBCT) is of importance to better identify patients who would benefit from blood conservation strategies as the risk of alloimmunization from RBCT has the potential to affect the fetus and newborn. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using hospital administrative data to identify trends and risk factors of RBCT in obstetric patients...
June 22, 2017: Transfusion
https://www.readbyqxmd.com/read/28643361/screening-for-del-phenotype-in-rhd-negative-indians
#4
Swati Kulkarni, Disha S Parchure, Vidya Gopalkrishnan, Manisha Madkaikar
BACKGROUND: DEL phenotype represents a very weak form of D variant detected only by adsorption and elution technique. DEL phenotype individuals mistyped as RhD-negative can lead to alloimmunization after transfusion or pregnancy. Molecular techniques have now been used to identify DEL variants. They are commonly encountered in the East Asian population with RHD(K409K) being the most frequent allele. RHD(M295I) is the most common DEL allele in Caucasians. As there is a paucity of data on DEL phenotype in the Indian population, the study aims to screen RhD negative individuals for two most common DEL mutations...
June 23, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28640792/alloimmunization-after-cryopreserved-arterial-allografts-in-a-patient-on-a-kidney-transplantation-waiting-list
#5
Cyril Garrouste, Eugenio Rosset, Fabienne Quainon, Julien Aniort, Anne Elisabeth Heng
No abstract text is available yet for this article.
July 2017: Transplantation
https://www.readbyqxmd.com/read/28639314/determinants-of-red-blood-cell-alloantibody-detection-duration-analysis-of-multiply-alloimmunized-patients-supports-peritransfusion-factors
#6
Lorette Noiret, Amy Slater, John M Higgins
BACKGROUND: Alloimmunization to red blood cells (RBCs) can cause serious transfusion reactions and complicate the search for compatible blood products. Alloantibodies can be detected for periods ranging from a few days to several years, yet the mechanisms controlling the duration of detectability remain unknown. We studied the detection durations in patients forming multiple antibodies to investigate whether the duration is more strongly determined by conditions present at the time of each transfusion (peritransfusion factors) or by more stable patient-specific factors likely to persist across transfusions...
June 21, 2017: Transfusion
https://www.readbyqxmd.com/read/28639307/anti-d-in-a-mother-hemizygous-for-the-variant-rhd-dnb-gene-associated-with-hemolytic-disease-of-the-fetus-and-newborn
#7
Kelli M Quantock, Genghis H Lopez, Catherine A Hyland, Yew-Wah Liew, Robert L Flower, Frans J Niemann, Arthur Joyce
BACKGROUND: Individuals with the partial D phenotype when exposed to D+ red blood cells (RBCs) carrying the epitopes they lack may develop anti-D specific for the missing epitopes. DNB is the most common partial D in Caucasians and the clinical significance for anti-D in these individuals is unknown. STUDY DESIGN AND METHODS: This article describes the serologic genotyping results and clinical manifestations in two group D+ babies of a mother presenting as group O, D+ with alloanti-D...
June 21, 2017: Transfusion
https://www.readbyqxmd.com/read/28630231/understanding-medication-nonadherence-after-kidney-transplant
#8
Thomas E Nevins, Peter W Nickerson, Mary Amanda Dew
Alloimmunity remains a barrier to long-term graft survival that necessitates lifelong immunosuppressive therapy after renal transplant. Medication nonadherence has been increasingly recognized as a major impediment to achieving effective immunosuppression. Electronic medication monitoring further reveals that nonadherence manifests early after transplant, although the effect is delayed. The etiology of nonadherence is multifactorial, with the strongest risk factors including past nonadherence and being an adolescent or young adult...
June 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28630094/type-i-ifn-is-necessary-and-sufficient-for-inflammation-induced-red-blood-cell-alloimmunization-in-mice
#9
David R Gibb, Jingchun Liu, Prabitha Natarajan, Manjula Santhanakrishnan, David J Madrid, Stephanie C Eisenbarth, James C Zimring, Akiko Iwasaki, Jeanne E Hendrickson
During RBC transfusion, production of alloantibodies against RBC non-ABO Ags can cause hemolytic transfusion reactions and limit availability of compatible blood products, resulting in anemia-associated morbidity and mortality. Multiple studies have established that certain inflammatory disorders and inflammatory stimuli promote alloimmune responses to RBC Ags. However, the molecular mechanisms underlying these findings are poorly understood. Type I IFNs (IFN-α/β) are induced in inflammatory conditions associated with increased alloimmunization...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628770/a-comparative-analysis-between-proteasome-and-immunoproteasome-inhibition-in-cellular-and-humoral-alloimmunity
#10
Theodoros Eleftheriadis, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Triggered by the successful administration of the proteasome inhibitor bortezomib in kidney transplant recipients with acute or chronic antibody-mediated rejection, we evaluated the effect of the proteasome inhibitor CEP-18770 and of the selective immunoproteasome inhibitor ONX-0914 on cellular and humoral alloimmunity. Cellular alloimmunity was assessed by cell proliferation in a two-way mixed lymphocyte reaction (MLR) with human peripheral blood mononuclear cells (PBMC). For assessing humoral alloimmunity we developed a method, where humoral alloimmunity was induced in one-way MLR...
June 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28628037/alloimmune-t-cells-in-transplantation
#11
Susan DeWolf, Megan Sykes
Alloimmune T cells are central mediators of rejection and graft-versus-host disease in both solid organ and hematopoietic stem cell transplantation. Unique among immune responses in terms of its strength and diversity, the T cell alloresponse reflects extensive genetic polymorphisms between allogeneic donors and recipients, most prominently within the major histocompatibility complex (MHC), which encodes human leukocyte antigens (HLAs) in humans. The repertoire of alloreactive T cell clones is distinct for every donor-recipient pair and includes potentially thousands of unique HLA/peptide specificities...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28620645/alloimmunity-but-not-viral-immunity-promotes-allograft-loss-in-a-mouse-model-of-polyomavirus-associated-allograft-injury
#12
Steven C Kim, Jun Wang, Ying Dong, David V Mathews, Joshua A Albrecht, Cynthia P Breeden, Alton B Farris, Aron E Lukacher, Mandy L Ford, Kenneth A Newell, Andrew B Adams
BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury...
June 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28620195/attenuation-of-cgvhd-by-c5a-c5ar-blockade-is-associated-with-increased-frequency-of-treg
#13
Yulian Wang, Peilong Lai, Xiaomei Chen, Chang He, Xin Huang, Suxia Geng, Chenwei Luo, Suijing Wu, Wei Ling, Liye Zhong, Zesheng Lu, Peng Li, Jianyu Weng, Xin Du
C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618324/stem-cells-an-emerging-novel-therapeutic-for-type-1-diabetes-mellitus
#14
Umang G Thakkar, Aruna V Vanikar, Hargovind L Trivedi
Stem cell based strategies are therapeutically potent for treating type-1 diabetes mellitus owing to their intrinsic regenerative capacity and immunomodulatory properties to arrest autoimmune β-cell destruction, preserve residual β-cell mass, facilitate endogenous regeneration, ameliorate innate/ alloimmune graft rejection, restore β-cell-specific unresponsiveness in absence of chronic immunosuppression and to reverse hyperglycemia.
April 19, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28615417/t-cell-restricted-notch-signaling-contributes-to-pulmonary-th1-and-th2-immunity-during-cryptococcus-neoformans-infection
#15
Lori M Neal, Yafeng Qiu, Jooho Chung, Enze Xing, Woosung Cho, Antoni N Malachowski, Ashley R Sandy-Sloat, John J Osterholzer, Ivan Maillard, Michal A Olszewski
Cryptococcus neoformans is a ubiquitous, opportunistic fungal pathogen but the cell signaling pathways that drive T cell responses regulating antifungal immunity are incompletely understood. Notch is a key signaling pathway regulating T cell development, and differentiation and functional responses of mature T cells in the periphery. The targeting of Notch signaling within T cells has been proposed as a potential treatment for alloimmune and autoimmune disorders, but it is unknown whether disturbances to T cell immunity may render these patients vulnerable to fungal infections...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28614804/in-vivo-kinetics-and-nonradioactive-imaging-of-rapidly-proliferating-cells-in-graft-versus-host-disease
#16
Nataliya P Buxbaum, Donald E Farthing, Natella Maglakelidze, Martin Lizak, Hellmut Merkle, Andrea C Carpenter, Brittany U Oliver, Veena Kapoor, Ehydel Castro, Gregory A Swan, Liliane M Dos Santos, Nicolas J Bouladoux, Catherine V Bare, Francis A Flomerfelt, Michael A Eckhaus, William G Telford, Yasmine Belkaid, Remy J Bosselut, Ronald E Gress
Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28604446/evolving-approaches-in-the-identification-of-allograft-reactive-t-and-b-cells-in-mice-and-humans
#17
James S Young, Christine McIntosh, Maria-Luisa Alegre, Anita S Chong
Whether a transplanted allograft is stably accepted, rejected or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft...
June 8, 2017: Transplantation
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#18
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28600054/prenatal-treatment-of-severe-fetal-hemolytic-disease-due-to-anti-m-alloimmunization-by-serial-intrauterine-transfusions
#19
Lin Li, Linhuan Huang, Guangping Luo, Yanmin Luo, Qun Fang
OBJECTIVE: Fetal hemolytic disease is a common cause of fetal hydrops and fetal morbidity and mortality. Despite its relatively low frequency, the anti-M IgG antibody is one of the causes of severe fetal anemia and intrauterine death; only a few cases have been reported. CASE REPORT: This is a case of a pregnant woman with a history of three intrauterine deaths. A diagnosis of severe fetal anemia attributed to anti-M alloimmunization was confirmed in her fifth pregnancy...
June 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28597520/the-impact-of-vaccination-on-rbc-alloimmunization-in-a-murine-model
#20
P Natarajan, M Santhanakrishnan, C A Tormey, J E Hendrickson
Emerging data in animal models and humans suggest that pathogen-associated and damage-associated molecular patterns variably impact RBC alloantibody formation. In this study, we tested the hypothesis that vaccinations may enhance immune responses to transfused RBCs. The Pneumovax23 vaccine decreased the magnitude of anti-KEL alloimmunization in a murine model, whereas the hepB vaccine did not impact the response; RBC transfusion did not alter immune responses to either vaccine. These data highlight the complexities of the intersection of innate and adaptive immunity and suggest that future studies investigating the pathways through which inflammation impacts alloimmunization are warranted...
June 8, 2017: Vox Sanguinis
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