Membrane progesterone receptors in human regulatory T cells: a reality in pregnancy.

OBJECTIVE: To provide evidence of the existence of membrane progesterone receptor alpha (mPRα) on regulatory T cells (Treg) in peripheral blood during pregnancy, postulating a possible explanation for the effect of progesterone on preterm birth. DESIGN: Cross-sectional study. SETTING: Tertiary Obstetric Department in a University Hospital. POPULATION: Healthy pregnant women. METHODS: Treg cells from peripheral blood samples were studied by flow cytometry using multiple monoclonal antibody expression. MAIN OUTCOME MEASURES: Evaluate the number and percentage of CD4(+) CD25(high) CD127(low) , the number and percentage of Treg cells among the total CD4(+) T cells, and the percentage and mean fluorescence intensity (MFI) of mPRα in that population, using several gating strategies. RESULTS: 43 peripheral blood samples were collected from healthy women during pregnancy, whose median gestational age was 28.7 ± 7.1 (16-40) weeks. The percentage of CD4(+) in the total lymphocytes was 43% (32-51) and the percentage of CD4(+) CD25(high) CD127(low) was 4.8% (1.6-5.9), with only 45% (16-72) of those cells expressing the intracellular marker FoxP3 (Treg cell pool). We confirmed the existence of mPRα in that specific population because 8.0% (2.02-33) of the Treg cells were marked with the specific monoclonal antibody, with an mPRα(+) MFI of 719 (590-1471). CONCLUSIONS: This research shows that Treg cells express mPRα during pregnancy, which might play an important role in immune modulation by progesterone.

Leptin and resistin in overweight patients with and without asthma

BACKGROUND: Excess body mass increases the risk of development of asthmatic symptoms and their severity and decreases the treatment effectiveness. One of the hypotheses explaining the link between the two diseases concerns the adipokines, hormones produced by adipose tissue with a proinflammatory character. The aim of this study was to compare the levels of the adipokines (leptin and resistin) between overweight asthmatic patients, asthmatic patients with normal weight and overweight patients without asthma. METHODS: 80 peripheral blood samples were collected from patients and blood serum extracted. Three groups were selected: overweight asthmatic patients (BMI ≥ 25), overweight patients without asthma and asthmatic patients with normal weight (BMI < 25). Waist circumference of the patients was measured (cut-off points were 80 cm for women and over 94 cm for men) and a skin prick test performed. Comparison of adipokine concentration between the 3 groups was made and association between these concentrations and the measurements was performed. RESULTS: Although the concentrations of both adipokines were slightly higher for overweight asthmatic patients compared to overweight healthy patients, these differences were not significant. A significant association was found between leptin concentration and both BMI (p < 0.01) and waist circumference (p < 0.01). A difference for this cytokine was also found between asthmatic and non-asthmatic female patients (p < 0.05). CONCLUSIONS: As expected overweight patients with BMI ≥ 25 and patients with increased waist circumference showed higher leptin levels. We suggest that the studied cytokines, with a stronger indication for leptin, can elicit asthmatic inflammation in obese phenotype of asthma that affects more frequently women

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Leptin and resistin in overweight patients with and without asthma.

BACKGROUND: Excess body mass increases the risk of development of asthmatic symptoms and their severity and decreases the treatment effectiveness. One of the hypotheses explaining the link between the two diseases concerns the adipokines, hormones produced by adipose tissue with a proinflammatory character. The aim of this study was to compare the levels of the adipokines (leptin and resistin) between overweight asthmatic patients, asthmatic patients with normal weight and overweight patients without asthma. METHODS: 80 peripheral blood samples were collected from patients and blood serum extracted. Three groups were selected: overweight asthmatic patients (BMI≥25), overweight patients without asthma and asthmatic patients with normal weight (BMI<25). Waist circumference of the patients was measured (cut-off points were 80cm for women and over 94cm for men) and a skin prick test performed. Comparison of adipokine concentration between the 3 groups was made and association between these concentrations and the measurements was performed. RESULTS: Although the concentrations of both adipokines were slightly higher for overweight asthmatic patients compared to overweight healthy patients, these differences were not significant. A significant association was found between leptin concentration and both BMI (p<0.01) and waist circumference (p<0.01). A difference for this cytokine was also found between asthmatic and non-asthmatic female patients (p<0.05). CONCLUSIONS: As expected overweight patients with BMI≥25 and patients with increased waist circumference showed higher leptin levels. We suggest that the studied cytokines, with a stronger indication for leptin, can elicit asthmatic inflammation in obese phenotype of asthma that affects more frequently women.

FoxP3, GATA-3 and T-bet expression in elderly asthma.

BACKGROUND: Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation while T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients. OBJECTIVE: To evaluate FoxP3, GATA-3 and T-bet gene expression under basal conditions and after in vitro activation in a group of elderly asthmatic compared with age-matched healthy individuals. METHODS: Thirty-two elderly asthmatics and 17 healthy elderly individuals were selected. Serum total IgE was measured, and peripheral blood mononuclear cells (PBMCs) were isolated and stimulated in vitro with anti-CD3/anti-CD28, followed by mRNA isolation. After reverse transcription, real-time quantitative PCR was performed and relative quantification was determined 2(-ΔΔCt)(2(-ΔΔCt) method). RESULTS: The mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2±6.8 vs. 4.8±3.8, 2.4±2.9 vs. 1.7±0.9 and 3.3±2.1 vs. 2.1±1.5, respectively. Healthy individuals showed significantly higher expression of FoxP3 and T-bet; asthmatics had a lower T-bet/GATA-3 ratio, higher serum IgE and a positive significant correlation between total IgE and GATA-3 expression. CONCLUSION AND CLINICAL RELEVANCE: Elderly asthmatic patients have lower FoxP3 mRNA expression in PBMC, which can be associated with the sustained inflammatory process and with the decreased immune tolerance by Treg cells. The T-bet deficiency and the correlation of GATA-3 expression with the increase of IgE are characteristics of long-lasting asthma. Changes related to the immunosenescence process could provide an explanation for the minor differences observed between the groups. It is important to clarify persistent modifications in long-lasting asthma in the elderly and adequate future therapeutic approaches.

Apoptosis and asthma in the elderly.

BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The persistence of airway inflammation depends on a decrease in apoptosis of T lymphocytes and eosinophils and survival of these activated cells. T lymphocytes expressing gamma delta receptors can be identified in human lungs and play an important role in immune defence against pathogens and in the regulation of chronic inflammation. Aging is associated with evidence of some immune dysregulation. OBJECTIVE: The aim of this study was to analyze the apoptosis receptors of T lymphocytes in long-lasting asthma, to establish their correlation with activation markers such as CD25+ and human leukocyte antigen (HLA)-DR+, and to analyze the gama delta T cell expression in this disease. METHODS: A group of 64 individuals (group A) who had had asthma for more than 30 years (mean age [+/-SD] 72 +/- 5 years) and 61 healthy individuals acting as controls--group B with 41 individuals (mean age 79 +/- 7 years) and group C with 20 individuals (mean age 38 +/- 12 years) were included in the study. All subjects underwent clinical evaluation and spirometric testing. Peripheral blood cells were stained with monoclonal antibodies anti-CD3, anti-CD4, anti-CD8, anti-CD25, anti-TCR gamma delta, anti-HLA-DR and anti-CD95. Statistical comparisons were performed between the asthmatics and the elderly control group and between the elderly control group and the adult control group. RESULTS: The average percentage of predicted forced expiratory volume in the first second was 73.6 gamma delta 25.3. The mean values of T cell receptors for asthma group A vs elderly control group B vs adult control group C respectively, were the following: CD3, 74.9+/-7 vs. 74.8 +/- 8.8 (P=ns) vs. 76.7 +/- 4.2 (P=ns); CD4, 48.8 +/- 8.7 vs. 43.5 +/- 10.2 (P=ns) vs. 44.8 +/- 3.8 (P=ns); CD8, 23.3 +/- 7.9 vs. 25.7 +/- 10.2 (P=ns) vs. 25.6 +/- 4.5 (P=ns); CD25, 14.3 +/- 5.9 vs. 22.4 +/- 7.8 (P = .0001) vs. 5.5 +/- 2.4 (P = .0001); TCR gamma delta, 2.8 +/- 2.1 vs. 4.1 +/- 3.3 (P < .05) vs. 4.6 +/- 2.1 (P=ns); HLA-DR, 18.4 +/- 9.2 vs. 17.8 +/- 5.9 (P=ns) vs. 15.4 +/- 5.1 (P=ns) and CD95, 49.3 +/- 13.7 vs. 52.6 +/- 12.1 (P=ns) vs. 13.8 +/- 10.8 (P = .0001). CONCLUSIONS: The immunological and inflammatory changes related to ageing may cause an increase in CD95 and CD25 T cell expression. In asthma, blood cells may express increased activation and apoptosis markers but in elderly patients taking steroids, these receptors remain within normal ranges. The number of gamma delta T cells may be lower in long-lasting asthma, and have a limited modulatory effect on allergic inflammatory reactions. The evaluation of patients with long-lasting asthma should take into account the immunological and inflammatory changes present in the elderly in order to avoid results being misinterpreted.

Elevated neopterin levels in non-allergic asthma.

Neopterin is synthesized by human monocyte-derived macrophages upon stimulation with interferon-gamma (IFN-gamma). Measurement of neopterin concentration is useful to monitor cell-mediated (Th1-type) immune activation. In this study, we aimed to analyze the behaviour of neopterin in long lasting asthma considering its role as a marker of the Th1 environment and to establish the distinction between patients belonging either to the allergic or the non-allergic population, particularly in the elderly where asthma is often under diagnosed. Therefore we evaluated allergic parameters such as skin prick tests, IgE and hemogram (eosinophils count), and we compared our findings with neopterin values found in an age-matched control population. A group of individuals older than 65 was selected. It included 64 asthmatic patients (mean age 72+/-5 years) and 41 healthy individuals (mean age 79+/-7 years). In our study population, 42 patients presented positive skin tests, mainly to house dust mites. All patients were clinically stable and presented an average percentage of predicted forced expiratory volume in the first second (FEV1) of 73.6+/-25.3 and predicted median expiratory flow percentage (MEF50) of 38.8+/-26.7. Blood cell counts showed statistically different mean values of eosinophils between allergic and non-allergic controls (5.42+/-4.7% versus 2.8+/-2.8%; p<0.04). IgE values were increased in allergic asthmatic patients when compared with non-allergic asthmatic patients (493.2+/-549.8IU/ml versus 85.3+/-194.4IU/ml; p=0.000). Allergic asthmatic patients presented mean neopterin levels similar to those found in the control group (2.4+/-2.8ng/ml versus 2.1+/-1.9ng/ml). In contrast, in non-allergic asthmatic patients these values were higher when compared with the control group (4.0+/-4.7ng/ml versus 2.1+/-1.9ng/ml). Neopterin levels were lower in allergic asthmatic patients when compared with non-allergic asthmatic patients (2.4+/-2.8ng/ml versus 4.0+/-4.7ng/ml). Within asthmatic patients, those with higher neopterin values (>2.1ng/ml) presented lower mean IgE values (IgE

The evaluation of neopterin and antioxidants in long lasting asthma.

Asthma is a condition characterised by a chronic immunoinflammatory response to different triggers. Neopterin (NPT) is synthesised by human macrophages upon stimulation with interferon-gamma and is also capable of enhancing the oxidative potential of reactive oxygen species. NPT is useful for the monitoring of cell-mediated (Th1-type) immune activation. This study analysed the behaviour of NPT in long lasting asthma, considering its role as a marker of Th1 environment. Allergic parameters (skin prick tests, Immunoglobin E (IgE), and eosinophil count) and NPT were evaluated in an asthmatic group and in a control group. We also analysed the C Reactive Protein (CRP) concentration, Total Antioxidant Status (TAS) and Superoxide Dismutase Enzyme (SOD) in both groups. A group of individuals aged over 65 years old was selected. It included 64 asthmatic patients (72+/-5 years) and 41 healthy individuals (79+/-7 years). Blood cell counts showed statistically different median values of eosinophils (5.42+/-4.7 vs 2.8+/-2.8;p<.04), IgE (493.2+/-549.8 vs 85.3+/-194.UI/ml; p=.000) and NPT was non-statistically decreased (2.4+/-2.8 vs 4.0+/-4.7 ng/ml) in allergic asthmatic patients when compared with non-allergic asthmatic patients. Both allergic and non-allergic asthmatic patients presented a statistically significant decreased expression of TAS (0.84+/-0.14/0.86+/-0.11 vs 0.91+/-0.10 mM) and SOD (584.8+/-108.7/595.6+/-235.9 vs 822.9+/-179.5) when compared with normal control subjects. Our results suggest macrophage involvement in asthma pathogenesis. The deficit in antioxidant defence impacts negatively on this disease. The increase of NPT values in non-allergic asthma consolidates these affirmations and mapping this parameter should be part of the work of an analytical study panel as it may lead to allergic asthma being distinguished from non- allergic asthma.