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Aims/hypothesis: Rapid and adequate islet revascularisation and restoration of the islet–extracellular matrix (ECM) interaction are significant factors influencing islet survival and function of the transplanted islets in individuals with type 1 diabetes. Because the ECM encapsulating the islets is degraded during islet isolation, understanding the process of revascularisation and engraftment afte

Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neo-epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore ag

Rationale, Aims, and Objectives: Primary health care often has overall responsibility for elderly patients and their medication treatment. This is a challenging task due to the issue of multiple caregivers, different systems for documentation and multimorbidity among the elderly. The multiprofessional project SÄKLÄK2 was developed to raise drug safety in Swedish primary health care, and this study

Scholars and practitioners are increasingly promoting so-called nature-based approaches for urban climate change adaptation. There is widespread consensus that they both support and require transdisciplinary approaches, notably by involving citizens in the change process and finding innovative ways to unite different actors’ efforts and capacities. However, there is little empirical evidence regar

The second-generation thrombopoietin (TPO) receptor agonists eltrombopag and romiplostim are potent activators of megakaryopoiesis and represent a growing treatment option for patients with thrombocytopenic hematological disorders. Both TPO receptor agonists have been approved worldwide for the treatment of children and adults with chronic immune thrombocytopenia. In the EU and USA, eltrombopag is

Treatment of autoimmune and inflammatory diseases typically involves immune suppression. In an opposite strategy, we show that administration of the highly inflammatory erythrocyte-specific antibody Ter119 into mice remodels the monocyte cellular landscape, leading to resolution of inflammatory disease. Ter119 with intact Fc function was unexpectedly therapeutic in the K/BxN serum transfer model o

Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Although acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy) and agouti-related peptide (Agrp) in adult mice or in mice homozygous for the anorexia (anx) mutation ca

Rationale: Effective and rapid bacterial clearance is a fundamental determinant of outcomes in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. Objectives: Because cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role ofDJ-1 in bacterial sepsis. Methods: We used cell and murine models with gain- A nd loss-offunction experiments, pla

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusionrelated fatalities and is characterized by the onset of acute respiratory distress within six hours following blood transfusion. In most cases, donor antibodies are suggested to be involved, however, the pathogenesis is poorly understood. A two-hit model is generally assumed to underlie TRALI pathogenesis where the fi

Several biological medicines derived from human and animal plasmas can effectively improve haemostasis in individuals with inherited or acquired defects in haemostasis. Factor VIII and factor VIII/vWF and factor IX concentrates are used to treat haemophilia A, von Willebrand disease and hemophilia B respectively. Cryoprecipitates are used to treat hypofibrinogenemia and von Willebrand disease wher

BACKGROUND: Anti-D treatment is effective in increasing platelet (PLT) counts in patients with autoimmune thrombocytopenic purpura (AITP); however, the exact mechanism of action is unknown. Previous results have suggested that anti-D-coated red blood cells (RBCs) affect reticuloendothelial system phagocytosis by stimulating agents (e.g., reactive oxygen species) that alter signaling pathways withi

Platelets express Toll-like receptor 4 (TLR4), and this has been shown to be responsible for the thrombocytopenia induced by lipopolysaccharide (LPS) administration in vivo. We studied the role of LPS in mediating platelet phagocytosis by THP-1 cells in vitro by flow cytometry. Opsonization of platelets with an IgG monoclonal (W6/32) antibody or with IgG autoantibody-positive sera from patients wi

The exact mechanism of action of IVIg in the amelioration of immune thrombocytopenic purpura (ITP) is still unclear. Studies have suggested that IVIg may function through the regulation of cytokines, including interleukin-1 receptor antagonist (IL-1Ra), an inhibitor of phagocytosis. Using a mouse model relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after exposure to IVIg,

Fetal and neonatal alloimmune thrombocytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin-deficient (β3-/-) mi

Toll-like receptors (TLRs) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) on invading microorganisms. Platelets also play a role in innate immunity, and we studied whether they express TLR. Results show that human and murine platelets variably expressed TLR2, TLR4, and TLR9 by flow cytometry and Western blotting. TLR4 expression wa

Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder in which autoantibodies are directed against an individual's own red blood cells (RBCs), leading to enhanced clearance through Fc receptor (FcR)-mediated phagocytosis. Although there is a large literature relating to clinical aspects of AIHA, relatively little work addresses how IgG autoantibodies are actually produced against RBC autoan

BACKGROUND: Immunoglobulin G (IgG) anti-platelet (PLT) immunity has been shown to be initiated by indirect allorecognition where recipient T cells recognize donor PLT antigens presented by class II molecules encoded by the major histocompatibility complex (MHC) on recipient antigen-presenting cells. To understand how the recipient's MHC class II molecules may influence PLT alloimmunity, immune res

The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were