Interleukin 3-induced GITR promotes the activation of human basophils.

Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2, IL-17RB and IL-2 receptors regulate the biology of basophils. However, the expression and function of IL-3-induced surface proteins on human basophils remain to be elucidated. We in this study aimed to identify new basophil activation regulators by transcriptomic analysis of IL-3-stimulated basophils. Gene expression microarray analysis of IL-3-treated basophils revealed 2050 differentially expressed genes, of which 323 genes encoded surface proteins including GITR. We identified that GITR was preferentially induced by IL-3 rather than anti-IgE, IL-33, fMLP and C5a. IL-3-induced GITR was suppressed by inhibitors targeting JAK2, PI3K and MEK1/2. Stimulation of IL-3-treated basophils by GITR enhanced the expression of IL-4 and IL-13. Moreover, IgE-mediated degranulation was enhanced by GITRL in the presence of IL-3. This transcriptomic analysis of IL-3-activated basophils helps to identify novel activation regulator. IL-3-induced GITR promoted the activation of basophils, adding new evidence supporting GITR as an important player in Th2-associated immune responses.

Interleukin 2 regulates the activation of human basophils.

Basophils are important effector cells in allergic disorders and anti-parasitic immune response. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identified that IL-2 induced the activation of human basophils in vitro to express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. This effect by IL-2 is confirmed by an upstream regulator analysis using Ingenuity pathway analysis. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be induced by IL-2 in human basophils rather than IL-3 or anti-IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely expressed IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils. This adds a new layer to support the importance of basophils in allergic disorders.

Estimation of the sensitivity and specificity of assays for screening antibodies to HIV: a comparison between the frequentist and Bayesian approaches.

Bayesian and frequentist methods have been applied rarely to the same sets of data for evaluating assays for screening antibodies to HIV, especially for assays with relatively high sensitivities and/or specificities of 100% compared with reference assays. In this study, 95% confidence intervals and 95% Bayesian credible intervals were calculated for sensitivity and specificity for the evaluation of the accuracy of HIV antibody assays using data from China, WHO UNAIDS, USA, Australia, Tanzania, and India. When the sensitivity and/or specificity were 100%, a Bayesian approach obtained reasonable interval estimates of assays for screening antibodies to HIV, whereas frequentist methods express objectively the accuracy of each individual assay. It is suggested that the two types of estimates be reported simultaneously to evaluate more comprehensively a set of highly accurate antibodies for HIV assays.

Evaluation of 30 commercial assays for the detection of antibodies to HIV in China using classical and Bayesian statistics.

The purpose of this study was to evaluate the 30 commercial HIV-antibody (HIV-Ab) assays in the nationwide assessment program of China using classical and Bayesian statistical methods. The classical estimates of sensitivity and specificity varied from 95.9% to 100% and from 94.6% to 100%, respectively. The proportions of assays with 100% sensitivity and with 100% specificity reached 63.3% (19/30) and 3.3% (1/30), respectively. Using the Bayesian logit hierarchical model, the overall estimates of sensitivity and specificity were 99.8% (95% Bayesian credible interval [BCI]: 99.4-100%) and 98.1% (95% BCI: 97.4-98.7%), respectively, for the 17 ELISAs under evaluation. For the 13 rapid assays, the corresponding overall estimates were reported to be 99.2% (95% BCI: 98.5-99.8%) and 98.4% (95% BCI: 97.8-98.9%), respectively. In addition, given the prevalences of HIV infection among the general population of China and the intravenous drug user group in China, the positive predictive values were estimated for each individual assay in the framework of the two schools of statistical thought. Furthermore, by comparing the two types of estimates, it is concluded that the two types of statistical methods were complementary for the evaluation of very accurate HIV-Ab assays.