Diagnostic performance of different criteria.

<p>*kU/l, NE: not estimable.</p><p>Diagnostic performance of different criteria.</p

Diagnostic accuracy of the specific/total IgE ratio for detecting reactive patients.

<p>Accuracy is presented both as sensitivity and specificity plot at increasing ratio levels (2A: left) and as a ROC curve (2B: right). The uncertainty of the specificity at 90% specificity is also shown as a vertical bar in the ROC curve.</p

Scatterplot of the sum of β-lactams vs. total IgEs.

<p>Both axes are on the log scale, enabling to plot the ratio index values as a straight, oblique line, given that the ratio of two variables equals a linear difference in their logs. Black filled symbols are reactive patients and empty symbols are non-reactive subjects. Triangles are subjects with specific/total IgE ratio above 0.002 and circles are those below this level. Subjects with non-measurable sum of β-lactam IgEs are plotted in two lines parallel to the x axis and below the detection threshold of 0.10 kUA/l. It can be seen that the subjects above the ratio are nearly all reactive or true positives (black triangles), while a substantial amount of false positives (black circles) is found below this ratio threshold for subjects with total IgE above 200 kU/l.</p

ROC curves analysis.

<p>ROC curves (with vertical line presenting the 95% confidence interval of sensitivity at 90% specificity) for imputed specific/total IgE ratio in the whole sample (left), as well as in subjects with total IgE values below (center) or above (right) total IgE values of 200 kU/l.</p

Clinical characteristics of analyzed patients.

<p>* confirmed by a positive skin testing to inhalant and/or food allergens. Total serum IgE were detected as described in Methods, values are reported as mean ± SE.</p><p>° patients who displayed a severe reaction affecting at least two organs with bronchospasm and/or hypotension.</p><p>Clinical characteristics of analyzed patients.</p

Smoothed distribution of the specific/total IgE ratio in reactive and non-reactive patients.

<p>Smoothed distribution of the specific/total IgE ratio in reactive and non-reactive patients.</p

Scatterplot of the sum of β-lactam vs. total IgEs for observed and imputed values.

<p>Observed values (bottom row) and imputed values (upper row) as explained in the Methods. Observed and imputed data for non-reactive patients (left column) tend to line just below the ratio index threshold oblique line corresponding to 0.002 cut-off. See text for comments.</p

Image_1_Efficacy and Safety of Mepolizumab (Anti-Interleukin-5) Treatment in Gleich’s Syndrome.tif

<p>Gleich’s syndrome (GS) is characterized by recurrent episodes of angioedema, increase in body weight, fever, hypereosinophilia, and elevated serum IgM. The exact etiology remains unclear. Currently, the only treatment strategy is the administration of high dose of steroids during the acute phases. We report the case of a 37-year-old man suffering from GS with recurrent episodes of angioedema, fever, hypereosinophilia [6,000/mm³ (45%)], and high eosinophil cationic protein (ECP) (>200 μg/l), treated with oral steroids during the acute phase (prednisone 50–75 mg/day), the dose of maintenance being 25 mg/day. No monoclonal components were identified, and genetic tests exclude mutations including Bcr/Abl, JAK2 V617F, c-KIT D816V, and FIP1L1-PDGFRA. Using Luminex technology, we observed higher serum levels of interleukin (IL)-5, CCL2, and CCL11 during the acute exacerbations in comparison with the clinical remission phases though CCL11 did not achieve statistical significance. The flow-cytometric analysis identified a CD3+ CD8− lymphocyte population with high frequency of IL-4-, IL-5-, and IL-13-producing cells. No clinical benefit was observed after therapeutic strategies with imatinib, interferon-α, cyclosporine-A, and azathioprine. Due to high IL-5 serum levels, an intravenous treatment with anti-IL-5 monoclonal antibody mepolizumab (750 mg every 4 weeks) was started. A reduction in the rate of exacerbation phases/year (10 ± 3 vs 2 ± 1; p < 0.005), in the eosinophils count both in percentage (28.8 ± 12.8 vs 9.8 ± 3.9; p < 0.001) and absolute value (2,737 ± 1,946 vs 782 ± 333; p < 0.001) were observed as well as the ECP serum levels (132.7 ± 62.7 vs 21 ± 14.2 μg/l; p < 0.05). The daily dose of prednisone was significantly reduced (25 vs 7.5 mg). Any adverse effects were recorded. To the best of our knowledge, this case is the first report of the disease successfully treated with mepolizumab, and it could represent a novel therapeutic strategy in GS.</p

Circulating levels of angiogenic T cells (Tang) correlate with severity of peripheral vascular damage in systemic sclerosis (SSc) patients.

<p><b>(A)</b> Representative CD31 versus CXCR4 dot plots of a SSc patient without digital ulcers (DU) and a SSc patient with DU. <b>(B)</b> Percentages of circulating CD3⁺CD31⁺CXCR4⁺ Tang cells in total CD3⁺ T cells from HC (n = 18), SSc patients without DU (n = 21) and SSc patients with DU (n = 18). <b>(C)</b> Percentages of circulating CD3⁺CD31⁺CXCR4⁺ Tang cells in total CD3⁺ T cells from HC (n = 18), SSc patients with early/active nailfold videocapillaroscopy (NVC) patterns (n = 20) and SSc patients with late NVC pattern (n = 19). Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Lines outside the boxes represent the 10th and the 90th percentiles. Circles indicate outliers. Differences were evaluated by Mann–Whitney U test.</p

Th1-Induced CD106 Expression Mediates Leukocytes Adhesion on Synovial Fibroblasts from Juvenile Idiopathic Arthritis Patients

<div><p>This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints.</p></div