Association between circulating MicroRNAs (hsa-miR-92a-1* and hsa-miR-454) and multiple sclerosis phenotypes and activity status.

Efficient diagnosis of multiple sclerosis (MS) disease along with early prediction of its progression will ultimately lead to better management, control of complications and improvement of therapeutic outcomes and patient's well-being. Blood based biomarkers like circulating microRNAs represent a non- invasive, fast, and easily measured markers with a promising potential. This work intended to assess the relative expression of circulating hsa-miR-454 and hsa-miR-92a-1* as a diagnostic and prognostic tool among Egyptian MS patients in terms of correlation to disease type and severity. hsa-miR-454 and hsa-miR-92a-1* relative expression was measured in the plasma of 31 MS patients, relapsing remitting MS (RRMS, n=21) and progressive MS (PMS, n=10) and 20 age and sex matched normal controls by using reverse transcription followed by real time PCR. Disease severity assessment was done in the form of patient expanded disability status scale (EDSS) evaluation. Relative expression of hsa-miR-454 and hsa-miR-92a-1* did not show a statistically significant difference between MS cases and controls. However, hsa-miR-454 was significantly higher among RRMS patients in comparison to PMS patients (P = 0.04). Additionally, both markers showed a statistically significant upregulation among patients in disease exacerbation in comparison to patients in remission (P = < 0.01) and both showed a negative correlation with EDSS. In conclusion, microRNAs may represent potential valuable non-invasive biomarkers for assessment of MS type (RRMS vs PMS), as well as for prediction of disease activity and severity in MS patients.

A comparative study of two angiogenic factors: vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack.

BACKGROUND: Angiogenesis is a prerequisite for airway remodeling in bronchial asthma. Several factors may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization. OBJECTIVES: (1) To determine the levels of vascular endothelial growth factor (VEGF) and angiogenin in sputum supernatants of asthmatic children during the acute attack and 6 weeks after start of therapy; and (2) to correlate their levels with the degree of asthma severity. SUBJECTS AND METHODS: Twenty asthmatic children with acute attack (mean age, 9.6 +/- 3.5 years [+/- SD]) and 12 sex- and age-matched healthy control children were enrolled in the study. Sputum supernatants were collected for determination of VEGF and angiogenin levels. Serum samples were withdrawn for IgE measurement. The above tests were performed using an enzyme-linked immunosorbent assay. The FEV1 was measured using spirometry. VEGF, angiogenin, and FEV1 estimations were repeated for asthmatic children 6 weeks after start of therapy. RESULTS: During the acute attack, asthmatic children had significantly higher levels of VEGF and angiogenin than in healthy control children (p < 0.001). VEGF and angiogenin levels showed more elevation with increase in asthma severity (p < 0.001). A significant positive correlation existed between both angiogenic factors (r = 0.98, p < 0.001). A negative significant correlation was found between FEV1 percentage of predicted and both VEGF (r = -0.99, p < 0.001) and angiogenin (r = -0.97, p < 0.001). A nonsignificant correlation was found between serum IgE and sputum VEGF (r = 0.09, p > 0.05). Although there was a significant decrease in the levels of both VEGF and angiogenin after 6 weeks of treatment with corticosteroid inhalation therapy, the levels did not reach normal control levels (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: Our results show that both VEGF and angiogenin levels were elevated in children with acute asthma. The study also suggests that increased severity of bronchial asthma in children is associated with the expression of both angiogenic factors, which are implicated in asthma pathogenesis. After 6 weeks of therapy, the levels of both angiogenic factors showed significant decrease.

Role of regulatory CD4+CD25+ Foxp3 T cells in bronchial asthma in Egyptian children.

CD4+CD25+high Foxp3 regulatory T (Treg) cells are known to play a key role in balancing immune response to maintain peripheral tolerance against harmless antigens or allergens. Defective immunological suppression by CD4+CD25+high Foxp3 Treg cells can be a cause of the inflammation that leads to an allergic condition such as asthma. The aims of the study are to (1) determine CD4+CD25+high Foxp3 Treg cells frequency in the peripheral blood of children with and without asthma; and (2) investigate the association between CD4+CD25+high Foxp3 Treg cells frequency with disease severity and corticosteroid therapy. Sixty asthmatic children with varying disease severity (20 mild, 20 moderate and 20 severe) were enrolled in the study. Severe asthmatic children were further subdivided into two groups, one on corticosteroid therapy and the other was not on corticosteroid. Twenty age and sex matched healthy children were enrolled as controls. Number of circulating CD4+CD25+high Foxp3 Tregs were measured using flow cytometry. Our finding demonstrates that children with asthma had a significant decrease of CD4+CD25high Foxp3 Treg cells and Tregs/T effectors ratio in peripheral blood compared to children without asthma. Patients with moderate asthma demonstrated lower frequency of CD4+CD25+high Foxp3 Treg cells compared to mild and severe asthmatic patients. Those on corticosteroid therapy revealed significant increase in CD4+CD25+high Foxp3 Treg cells and decrease in T effectors. It is concluded that asthmatic children have decreased number of CD4+CD25+high Foxp3 Treg cells leading to increase in effectors cells which mediate inflammation in the airways. Corticosteroid therapy plays a role in elevating number of CD4+CD25+high Foxp3 Treg cells and maintaining its suppressor function.

Effect of surgically-induced weight loss on inflammatory mediators and peripheral blood monocyte CD11b expression in morbid obesity.

Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers. Expression and release of inflammation-related adipokines, generally, rise as adipose tissue expands. In the present study we evaluated the level of serum mediators concerned in inflammation and monocyte activation (TNF-alpha, hs-CRP, MCP-1) together with percentage of CD11-b expression on monocytes in a group of morbidly obese individuals (n = 20) before and (3-6 months) after restrictive surgery, and in 15 healthy normal weight individuals. Serum MCP-1, TNF-alpha and hs-CRP were assayed by enzymatic immunoassay, while the percentage of CD11b expression on monocytes was assayed by flow cytometry. The total lipid profile and random blood glucose levels were also assessed. Morbidly obese individuals ( before surgical weight loss) had significantly increased levels of MCP-1, TNF-alpha, hs-CRP, CD11b expression on monocytes as compared to controls (P < 0.01). Levels of MCP-1, TNF-alpha, hs-CRP were significantly decreased 3 to 6 months after restrictive surgery than before the operation (P < 0.01). hs-CRP, MCP-1 and TNF-alpha were positively correlated versus each other. TNF-alpha and hs-CRP also showed positive correlation with the body mass index. Our data suggested that the studied serum and monocyte parameters may link obesity with systemic inflammation and metabolic disorders. The interactions of MCP-1, CD11b and other inflammatory parameters might provide the basis for development of new therapies for this syndrome.