Increased expression of T-helper cell activation markers in peripheral blood of children with atopic asthma

Abstract

Background: Activated T-helper (CD4) cells have been implicated to contribute to the pathogenesis of bronchial asthma. However, the profile of circulating CD4 subsets in relation to disease activity and asthma severity is unclear.
Objective: To study the dynamic changes in peripheral blood CD4 cells expressing the activation markers naïve/memory (CD45RA/CD45RO) and interleukin–2 light chain receptor (CD25) in asthmatic children during and after resolution of acute asthma attacks and to determine whether the expression of these activation markers would be of value in monitoring asthma severity and the response to glucocorticoid inhalation.
Methods: Peripheral blood samples were obtained from 20 asthmatic children aged between 0.5 and 9 years (mean±SD: 4.37±2.37 years) with acute asthma attacks, 10 children with lower respiratory tract infection and 20 healthy, age-matched subjects. CD4 cells expressing CD45RA, CD45RO, CD45RA+RO+ and CD25 were analyzed by dual flow cytometry and serum IgE was measured by ELISA. In asthmatic children, the measurements were repeated after the resolution of acute attacks.
Results: During acute asthma attacks, the percentages of CD45RA, CD45RO, CD45RA+RO+ and CD25 were significantly increased as compared to the control group (p<0.05 for CD45RA and <0.0001 for the other 3 subsets). After resolution of asthma attacks, a significant reduction of all subsets was noticed and the percentages of CD45RA and CD45RO decreased to normal values while those of CD45RA+RO+ and CD25 remained significantly higher than the controls (p<0.05 for each marker). Unlike healthy children and patients with acute lower respiratory infections, asthmatic children showed increased CD45RO/CD45RA ratio (>1) and a significant increase of the percentage of CD45RA+RO+. During acute asthma attacks, patients with severe persistent asthma showed the highest percentages of all T- helper subsets when compared to those with moderate or mild persistent asthma. Positive correlations were found between serum IgE levels and both CD45RO and CD25 (r = 0.962, p<0.001 and 0.882, p<0.05 respectively) during acute asthma attacks and these correlations remained significant in remission (r = 0.632, p<0.05 and 0.589, p<0.05 respectively). Glucocorticoid inhalation therapy induced a significant reduction in the percentage of CD45RO, CD45RA+RO+ and CD25.
Conclusion: Peripheral blood T-helper cell activation markers are reliable indicators for monitoring disease activity and severity of asthma. The reversed ratio of memory/ naïve T-helper cells together with the presence of a clone of cells co-expressing both naive and memory surface markers feature atopic asthma from acute lower respiratory infections. Glucocorticoid inhalation therapy induces a significant inhibition of peripheral blood T-helper cell activation markers.

Key words: Children, atopic asthma, T-helper cell subsets, glucocorticoid inhalation, lower respiratory infections, CD45RO, CD45RA, CD25.