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Cees van Kooten, Ton J Rabelink, Johan W de Fijter, Marlies E J Reinders
PURPOSE OF REVIEW: Progress in the improvement of short-term and long-term outcomes of kidney transplantation seems to have reached a plateau, partially due to consequences of very efficient, but nonspecific immunosuppressive drugs. In recent years, various forms of cell therapy, including the use of mesenchymal stromal cells, have been put forward as an alternative strategy for more defined therapy. It is thought that these therapies will not only allow controlled tapering of immunosuppressive medication, but might bring us also closer to the ambition of generating donor-specific immune regulation and tolerance...
October 15, 2016: Current Opinion in Organ Transplantation
Marta Ferro, Hada C Macher, Pilar Noguerol, Pilar Jimenez-Arriscado, Patrocinio Molinero, Juan M Guerrero, Amalia Rubio
Fetal and Neonatal alloimmune thrombocytopenia (FNAIT) is a condition which could occur when pregnant women develop an alloimmunization against paternally inherited antigens of the fetal platelets. Approximately 80 % of FNAIT cases are caused by anti-HPA-1a, about 15 % by anti-HPA-5b and 5 % by other HPA antibodies. Only 2 % of the total population is HPA-1a negative (HPA-1b1b). The HPA-1a allele differs by one single nucleotide from HPA-1b allele, yet it represents around 27 % of total severe thrombocytopenias...
2016: Advances in Experimental Medicine and Biology
Edward Tuddenham
The declarative title is a fair summary of research described in this paper (Targeting Factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice)(10) , is a fair summary of research described in this paper, which is itself the 14th in a series from the group of researchers led by Montgomery who, since 2003 have progressively advanced the idea of storing factor VIII in platelets to treat hemophilia A. Why, one might ask, would one do such a thing when evolution has selected endothelial cells as both the site for synthesis and release of factor VIII complexed with Von Willebrand factor to provide the cofactor when and where needed?(1,2) The answer lies in the unfortunate fact that a high proportion of patients with hemophilia develop resistance to factor VIII due to alloimmunity to the protein, which is foreign to their immune system, leading to production of inhibitory antibodies to the cofactor...
October 17, 2016: Journal of Thrombosis and Haemostasis: JTH
Susanna Sainio, Kaija Javela, Jarno Tuimala, Katri Haimila
Lack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Despite the long-known association between the HLA-DRB3*01:01 allele and human platelet antigen 1a (HPA-1a) alloimmunisation, maternal human leucocyte antigen (HLA) typing has been of little clinical value. Recently, other DRB3 allele variants have been suggested to predict the severity of FNAIT. In this nationwide population-based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA-1a-immunisation...
October 17, 2016: British Journal of Haematology
Lindert Benedictus, Charlotte R Bell
Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for major-histocompatibility class I antigens are transferred from the mother to the calf via colostrum, leading to profound depletion of peripheral blood and bone marrow cells that is often fatal. Areas covered: Pubmed and Web of Science were used to search for literature relevant to BNP and the use of allogeneic vaccine cell lines...
October 17, 2016: Expert Review of Vaccines
Rohini Prashar, K K Venkat
Kidney transplantation is well established as the best treatment option for end-stage kidney disease. It confers not only a better quality of life but also a significant survival advantage compared to dialysis. However, despite significant improvement in short-term kidney transplant graft survival over the past three decades, long-term graft survival remains suboptimal. Concerns about the possible contribution of chronic calcineurin inhibitor (CNI) nephrotoxicity to late allograft failure and other serious adverse effects of currently used immunosuppressive agents (especially corticosteroids) have led to increasing interest in developing regimens which may better preserve kidney allograft function and minimize other immunosuppression-related problems without increasing the risk of rejection...
September 2016: Advances in Chronic Kidney Disease
Hannah B Anastasio, Maureen Grundy, Meredith L Birsner, Karin J Blakemore
BACKGROUND: Gestational alloimmune liver disease, a form of profound liver failure in the newborn, is the main underlying cause of the entity formerly known as neonatal hemochromatosis. Antepartum maternal intravenous immunoglobulin (IVIG) has been shown to prevent gestational alloimmune liver disease, which otherwise has a recurrence risk above 90% in subsequent pregnancies. CASE: A 30-year-old woman, gravida 3 para 0120, presented early in gestation. Her previous pregnancy had been complicated by fetal growth restriction, oligohydramnios, and ultimately fatal fulminant neonatal liver failure...
October 6, 2016: Obstetrics and Gynecology
Prabitha Natarajan, Jingchun Liu, Manjula Santhanakrishnan, David R Gibb, Lewis M Slater, Jeanne E Hendrickson
BACKGROUND: Few therapeutic options currently exist to prevent or to mitigate transfusion-associated red blood cell (RBC) alloimmunization. We hypothesized that bortezomib, a proteasome inhibitor currently being utilized for HLA alloantibody and ADAMTS13 autoantibody reduction, may be beneficial in a transfusion setting. Herein, we utilized a reductionist murine model to test our hypothesis that bortezomib would decrease RBC alloimmune responses. STUDY DESIGN AND METHODS: Wild-type mice were treated with bortezomib or saline and transfused with murine RBCs expressing the human KEL glycoprotein...
October 13, 2016: Transfusion
Julian Pulecio, Oriol Alejo-Valle, Sandra Capellera-Garcia, Marianna Vitaloni, Paula Rio, Eva Mejía-Ramírez, Ilaria Caserta, Juan A Bueren, Johan Flygare, Angel Raya
Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41(+), display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro...
October 11, 2016: Cell Reports
Marije M Kamphuis, Heidi Tiller, E S van den Akker, Magnus Westgren, Eleonor Tiblad, Dick Oepkes
OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome...
October 12, 2016: Fetal Diagnosis and Therapy
Luis Ibáñez-Samaniego, Magdalena Salcedo, Javier Vaquero, Rafael Bañares
De novo autoimmune hepatitis (DAIH) is a rare clinical condition with features that resemble those of autoimmune hepatitis in patients undergoing liver transplantation (LT) for non-autoimmune liver disease. The diagnosis of this entity has been based on the presence of biochemical and histological patterns similar to those observed in the primary autoimmune hepatitis, although several considerations must be taken into account. The impact of DAIH on graft survival is relevant, and early diagnosis and treatment is associated with a good long-term outcome...
October 6, 2016: Liver Transplantation
Carolien Zwiers, Irene T M Lindenburg, Frans J C M Klumper, Masja de Haas, Dick Oepkes, Inge L van Kamp
BACKGROUND: maternal alloimmunization to fetal red blood cell antigens is a major cause of fetal anemia, which in untreated cases can lead to hydrops and perinatal death. The cornerstone of the management during pregnancy is intrauterine intravascular blood transfusion. Although this procedure is considered to be relatively safe, (procedure-related) complications continue to occur. OBJECTIVES: to evaluate procedure-related complications and perinatal loss rates of intrauterine transfusion and changes over time, aiming to identify factors leading to improved outcome...
October 5, 2016: Ultrasound in Obstetrics & Gynecology
Maria Therese Ahlen, Anne Husebekk, Ida Løken Killie, Bjørn Skogen, Tor Brynjar Stuge
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a pregnancy-related condition caused by maternal antibodies binding an alloantigen on fetal platelets. In most cases the alloantigen is formed by a single amino acid, integrin β3 Leu33, referred to as human platelet antigen-1a (HPA-1a). Production of anti-HPA-1a antibodies likely depends on CD4(+) T cells that recognize the same alloantigen in complex with the HLA-DRA/DRB3*01:01 molecule. While this complex is well characterized, T cell recognition of it is not...
September 8, 2016: JCI Insight
R Phuangtham, A Romphruk, C Puapairoj, C Leelayuwat, A V Romphruk
OBJECTIVES: A comparative study of allele frequencies at HPA-1 to -6 and HPA-15 in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais (NET) is presented. BACKGROUND: Human platelet antigens (HPAs) are clinically important in several immune platelet disorders, including foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet transfusion refractoriness (PTR). The knowledge of antigen frequencies in a population is essential for the evaluation of patients suffering from immune-mediated platelet disorders...
October 3, 2016: Transfusion Medicine
Jingchun Liu, Manjula Santhanakrishnan, Prabitha Natarajan, David R Gibb, Stephanie C Eisenbarth, Christopher A Tormey, Alexa J Siddon, Sean R Stowell, Donald R Branch, Jeanne E Hendrickson
RBC alloimmunization is a serious complication of transfusion or pregnancy. Despite the widespread use of RhIg to prevent pregnancy associated anti-D alloimmunization, its mechanism of action remains elusive. We have previously described a murine model in which immunoprophylaxis with polyclonal anti-KEL sera prevents alloimmunization in wild type recipients transfused with transgenic murine RBCs expressing the human KEL glycoprotein. To investigate the mechanism of action, we have now evaluated the outcome of immunoprophylaxis treatment in mice lacking Fcγ receptors (FcγR), complement (C3), both, or none...
September 29, 2016: Blood
Helena Sá, Rita Leal, Manuel Santos Rosa
To deride the hope of progress is the ultimate fatuity, the last word in poverty of spirit and meanness of mind. There is no need to be dismayed by the fact that we cannot yet envisage a definitive solution of our problems, a resting-place beyond which we need not try to go. -P.B. Medawar, 1969* [Formula: see text] Thomas E. Starlz, also known as the Father of Clinical Transplantation, once said that organ transplantation was the supreme exception to the rule that most major advances in medicine spring from discoveries in basic science [Starzl T...
September 28, 2016: International Reviews of Immunology
Dimitri Poddighe, Elena Virginia, Marco Nedbal, Annarosa Soresina, Paola Bruni
A male newborn developed a post-natal cytomegalovirus (CMV) infection, arising in the clinical setting of congenital thrombocytopenia, which was diagnosed as being alloimmune. The evidence of active CMV infection in an infant showing slow-resolution lower airways infection, persistent neonatal and low platelet volume thrombocytopenia, and diffuse eczema (associated to very high levels of serum immunoglobulin E) led to the diagnosis of Wiskott-Aldrich syndrome (WAS) before the third month of life, despite the presence of several confounding clinical factors...
September 1, 2016: Le Infezioni in Medicina
Gi Su Lee, Joon Cheol Park, Jeong Ho Rhee, Jong In Kim
OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation...
September 2016: Obstetrics & Gynecology Science
Abhinav Arneja, Juan E Salazar, Wenyu Jiang, Jeanne E Hendrickson, James C Zimring, Chance John Luckey
No abstract text is available yet for this article.
August 4, 2016: Haematologica
Wensheng Zhang, Vijay S Gorantla, Phil G Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E Weiss, Xin Xiao Zheng, Mario G Solari
Pancreatic islet transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor islets and need for long-term multi-drug immunosuppression to prevent alloimmune islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and co-transplanted with allogeneic islets under the renal capsule to create an immunoregulatory microenvironment around the islet allograft...
September 20, 2016: Diabetes
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