Proof of concept pilot study: prevalence of grass virus infection and the potential for effects on the allergenic potency of pollen.

BACKGROUND: Wild plants harbour a variety of viruses and these have the potential to alter the composition of pollen. The potential consequences of virus infection of grasses on pollen-induced allergic disease are not known. METHODS: We have collected pollen from Dactylis glomerata (cocksfoot; a grass species implicated as a trigger of allergic rhino-conjunctivitis) from Wytham Wood, Oxfordshire UK. Extracts were prepared from pollen from uninfected grass, and from grass naturally infected by the Cocksfoot streak potyvirus (CSV). Preparations of pollen from virus-infected and non-infected grasses were employed in skin testing 15 grass pollen-allergic subjects with hayfever. Allergen profiles of extracts were investigated by Western blotting for IgE with sera from allergic subjects. RESULTS: The prevalence of CSV infection in cocksfoot grasses sampled from the study site varied significantly over an eight-year period, but infection rates of up to 70% were detected. Virus infection was associated with small alterations in the quantities of pollen proteins detected by polyacrylamide gel electrophoresis, and in the patterns of allergens identified by Western blotting with IgE from grass pollen allergic subjects. For individual subjects there were differences in potencies of standardised extracts of pollen from virus-free and virus-infected plants as assessed by skin testing, though a consistent pattern was not established for the group of 15 subjects. CONCLUSION: Infection rates for CSV in cocksfoot grass can be high, though variable. Virus-induced alterations in components of grass pollen have the potential to alter the allergenic potency.

Free secretory component from cystic fibrosis sputa displays the cystic fibrosis glycosylation phenotype.

Secretory IgA contributes to humoral defense mechanisms against pathogens targeting mucosal surfaces, and secretory component (SC) fulfills multiple roles in this defense. The aims of this study were to quantify total SC and to analyze the form of free SC in sputa from normal subjects, subjects with asthma, and subjects with cystic fibrosis (CF). Significantly higher levels of SC were detected in CF compared with both other groups. Gel filtration chromatography revealed that SC in CF was relatively degraded. Free SC normally binds interleukin (IL)-8 and inhibits its function. However, in CF sputa, IL-8 binding to intact SC was reduced. Analysis of the total carbohydrate content of free SC signified overglycosylation in CF compared with normal subjects and subjects with asthma. Monosaccharide composition analysis of free SC from CF subjects revealed overfucosylation and undersialylation, in agreement with the reported CF glycosylation phenotype. SC binding to IL-8 did not interfere with the binding of IL-8 to heparin, indicating distinct binding sites on IL-8 for negative regulation of function by SC and heparin. We suggest that defective structure and function of SC contribute to the characteristic sustained inflammatory response in the CF airways.

Growth factors in cystic fibrosis - when more is not enough.

In the airways of patients with cystic fibrosis, repeated cycles of infection and inflammation are responsible for bronchial wall thickening, a major determinant of loss of FEV(1) and progressive damage to the small and large airways. Proteolytic degradation of elastin, collagen and fibronectin fibrils in the tissue matrix leads to the loss of normal tissue architecture and the development of bronchiectasis, the most commonly observed morphological change on high-resolution computed tomography examination. We have reviewed the evidence for increased expression of growth factors (TGF, HGF, FGF, EGF, VEGF) and activation of tissue repair processes in cystic fibrosis. Significantly higher concentrations of the growth factors compared with normal do not appear to prevent or reverse structural remodelling in the airways. The reasons why this process appears to be ineffective are discussed and we speculate on alternative strategies that might have a significant impact on the observed structural changes.