6 research outputs found

    Clinical and laboratory aspects of common variable immunodeficiency

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    Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective antibody production, recurrent infections, most notably of the respiratory tract, autoimmune phenomena and cancer. Some CVID patients may also present disturbances of the cellular immune response such as a decrease in the number and proportion of different lymphocyte populations, diminished lymphoproliferative response to mitogens and antigens, altered production of cytokines, and deficient expression of cell-surface molecules. Most Brazilian CVID patients included in this study show a decrease in T and B lymphocyte counts in the peripheral blood. Furthermore, their lymphocytes are more susceptible to apoptosis following activation than normal individuals, and they have a decrease in the expression of activation molecules like CD25, CD69, CD40L and CD70. Moreover, they show a decreased synthesis of IL-4 and IL-5 in comparison with normal individuals. The increase in susceptibility to apoptosis following activation, may also be responsible for the decrease in the expression of activation molecules and CD40L, decrease in Th2 cytokines synthesis, and in the number of T and B circulating cells. In this study we discuss some of these immunological disturbances correlating them to the patients' clinical features and comparing our patients' findings to the literature

    Inversion of the Vδ1 to Vδ2 γδ T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion.

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    Common variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on γδ T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ T cells was found to be increased in CVID (median 0.60% vs 2.64%, P \u3c0.01 and 7.5 vs 39, P \u3c0.01 respectively), while they were decreased for Vδ2 γδ T cells (median, 2.36% vs 0.74%,P \u3c0.01 and 37.8 vs 13.9, P \u3c0.01 respectively) resulting in an inversion of the Vδ1 to Vδ2 ratio (0.24 vs 1.4, P \u3c0.001). Markers of immune activation were elevated on all subsets of γδ T cells, and HLA-DR expression was associated with an expansion of Vδ1 γδ T cells (r = 0.73, P = 0.003). Elevated PD-1 expression was found only on Vδ2 γδ T cells (median 1.15% vs 3.08%, P \u3c0.001) and was associated with the decrease of Vδ2 γδ T cells (r = −0.67, P = 0.007). IVIg had no effect on the frequency of Vδ1 and Vδ2 γδ T cells or HLA-DR expression, but alleviated CD38 expression on Vδ1 γδ T cells (median MFI 965 vs 736, P \u3c0.05). These findings suggest that immunological perturbations of γδ T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy

    Initial invasive or conservative strategy for stable coronary disease

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    BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used

    Health-status outcomes with invasive or conservative care in coronary disease

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    BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

    Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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