Antibodies to Serine Proteases in the Antiphospholipid Syndrome

It is generally accepted that the major autoantigen for antiphospholipid antibodies (aPL) in the antiphospholipid syndrome (APS) is β2-glycoprotein I (β2GPI). However, a recent study has revealed that some aPL bind to certain conformational epitope(s) on β2GPI shared by the homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Importantly, some serine protease–reactive aPL correspondingly hinder anticoagulant regulation and resolution of clots. These results extend several early findings of aPL binding to other coagulation factors and provide a new perspective about some aPL in terms of binding specificities and related functional properties in promoting thrombosis. Moreover, a recent immunological and pathological study of a panel of human IgG monoclonal aPL showed that aPL with strong binding to thrombin promote in vivo venous thrombosis and leukocyte adherence, suggesting that aPL reactivity with thrombin may be a good predictor for pathogenic potentials of aPL

Web interface-supported transmission risk assessment and cost-effectiveness analysis of postdonation screening: a global model applied to Ghana, Thailand, and the Netherlands

BACKGROUND: The goal of our research was to actively involve decision makers in the economic assessment of screening strategies in their region. This study attempted to accomplish this by providing an easy-to-use Web interface at http://www.bloodsafety.info that allows decision makers to adapt this model to local conditions. STUDY DESIGN AND METHODS: The cost-effectiveness was compared of 1) adding antigen screening to antibody screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 2) adding nucleic acid amplification testing (NAT) on hepatitis B virus (HBV), HCV, and HIV in minipool ( pool of 6 [MP6] and 24 [MP24]) to antibody screening and hepatitis B surface antigen ( HBsAg) screening; and 3) individual-donation NAT on HBV, HCV, and HIV to antibody screening and HBsAg screening for Ghana, Thailand, and the Netherlands. RESULTS: The combination of HCV antibody-antigen combination (combo) and HIV combo added to antibody screening in Ghana and Thailand was cost-effective according to the WHO criteria. MP24-NAT screening in Ghana was also cost-effective. MP24-NAT on HBV, HCV, and HIV was not cost-effective compared to the other screening strategies evaluated for the Netherlands. Large regional differences in cost-effectiveness were found for Thailand. CONCLUSION: The young transfusion recipient population of Ghana in combination with a high risk of viral transmission yields better cost-effectiveness for additional tests. The advanced age of the transfused population of the Netherlands and a small risk of viral transmission gives poor cost-effectiveness for more sensitive screening techniques. It was demonstrated that a global health economic model combined with a Web interface can provide easy access to risk assessment and cost-effectiveness analysis

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC