Search results for " Antiphospholipid"
showing 10 items of 26 documents
Biosensor Analysis of β2-Glycoprotein I–Reactive Autoantibodies: Evidence for Isotype-Specific Binding and Differentiation of Pathogenic from Infecti…
2007
Abstract Background: For the laboratory diagnosis of the antiphospholipid syndrome (APS) we developed a biosensor with the ability to distinguish between disease-relevant anti-β2-glycoprotein I (β2GPI) autoantibodies (anti-β2GPI) and pathogen-specific β2GPI cross-reactive antibodies that occur transiently during infections. Methods: We used a surface plasmon resonance (SPR) biosensor device. For the detection of anti-β2GPI in serum samples, affinity-purified human β2GPI was covalently attached to a functionalized n-alkanethiol self-assembling monolayer on the biosensor chip. After verifying the specificity of the biosensor system with a panel of monoclonal antibodies to β2GPI, we analyzed s…
Tissue factor pathway inhibitor primes monocytes for antiphospholipid antibody-induced thrombosis
2019
Antiphospholipid antibodies (aPLs) with complex lipid and/or protein reactivities cause complement-dependent thrombosis and pregnancy complications. Although cross-reactivities with coagulation regulatory proteins contribute to the risk for developing thrombosis in patients with antiphospholipid syndrome, the majority of pathogenic aPLs retain reactivity with membrane lipid components and rapidly induce reactive oxygen species-dependent proinflammatory signaling and tissue factor (TF) procoagulant activation. Here, we show that lipid-reactive aPLs activate a common species-conserved TF signaling pathway. aPLs dissociate an inhibited TF coagulation initiation complex on the cell surface of m…
RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues
2006
In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could co…
Complement C5 but not C3 is expendable for tissue factor activation by cofactor-independent antiphospholipid antibodies
2018
The complement and coagulation cascades interact at multiple levels in thrombosis and inflammatory diseases. In venous thrombosis, complement factor 3 (C3) is crucial for platelet and tissue factor (TF) procoagulant activation dependent on protein disulfide isomerase (PDI). Furthermore, C5 selectively contributes to the exposure of leukocyte procoagulant phosphatidylserine (PS), which is a prerequisite for rapid activation of monocyte TF and fibrin formation in thrombosis. Here, we show that monoclonal cofactor-independent antiphospholipid antibodies (aPLs) rapidly activate TF on myelomonocytic cells. TF activation is blocked by PDI inhibitor and an anti-TF antibody interfering with PDI bin…
The presence of infection-related antiphospholipid antibodies in infective endocarditis determines a major risk factor for embolic events.
1999
Abstract OBJECTIVES The impact of infection-associated antiphospholipid antibodies (APA) on endothelial cell activation, blood coagulation and fibrinolysis was evaluated in patients with infective endocarditis with and without major embolic events. BACKGROUND An embolic event is a common and severe complication of infective endocarditis. Despite the fact that APAs are known to be associated with infectious diseases, their pathogenic role in infective endocarditis has not been clearly defined. METHODS The relationship among the occurrence of major embolic events, echocardiographic vegetation size, endothelial cell activation, thrombin generation, fibrinolysis and APA was examined in 91 patie…
Antiphospholipid antibodies in pediatric patients with prolonged activated partial thromboplastin time during infection.
2005
Abstract Objective To investigate the close association between different antiphospholipid antibodies (aPL) caused by infection and their appearance together with a prolonged activated partial thromboplastin time (aPTT). Methods Sera from 122 children were evaluated in this study. Thirty-seven children with mild to medium prolonged aPTT (>37.2 s) and elevated C-reactive protein (CRP) levels during various forms of infections (group 2), 18 children without infections (group 3) but with mild to medium prolonged aPTT and 13 children with infections (group 4) and with elevated CRP-level as well as a control group (group 1) of 54 patients without any infection and normal aPTT and negative CRP le…
Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19
2021
Abstract Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndro…
Pathogenic Role of Complement in Antiphospholipid Syndrome and Therapeutic Implications
2018
Antiphospholipid syndrome (APS) is an acquired autoimmune disease characterized by thromboembolic events, pregnancy morbidity, and the presence of antiphospholipid (aPL) antibodies. There is sound evidence that aPL act as pathogenic autoantibodies being responsible for vascular clots and miscarriages. However, the exact mechanisms involved in the clinical manifestations of the syndrome are still a matter of investigation. In particular, while vascular thrombosis is apparently not associated with inflammation, the pathogenesis of miscarriages can be explained only in part by the aPL-mediated hypercoagulable state and additional non-thrombotic effects, including placental inflammation, have b…
Human parvovirus B19 infection and antiphospholipid antibodies
2007
Erythema infectiosum is the main manifestation of human parvovirus B19 infections. Further B19-related diseases commonly associated with the acute infection are flue-like symptoms, transient aplastic crisis, transient arthralgias, leukopenia and thrombocytopenia, spontaneous abortion and hydrops fetalis in pregnant women. Hepatitis, myocarditis, meningitis, encephalitis as well as pure red cell anemia may occur occasionally. In addition parvovirus B19 infections have been frequently described as cause or trigger of various forms of autoimmune diseases affecting all blood cell lines, joints, connective tissue, uvea, large and small vessels. Molecular mimicry may be one major contribution to …
Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?
2021
Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly ev…