Sublingual immunotherapy alters salivary IgA and systemic immune mediators in timothy allergic children.

BACKGROUND: Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis. METHODS: From children included in the GRAZAX® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods. RESULTS: GRAZAX® -treated children exhibited significantly higher levels of Phl p 1-specific salivary IgA and serum IgG4 , along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation. Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters. CONCLUSION: Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction.Funding agencies:  Research Council for South-East Sweden; University Hospital of Linkoping, Sweden</p

The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation

Abstract Asthma is characterised by chronic airway inflammation, airway obstruction and hyper-responsiveness. The inflammatory cascade in asthma comprises a complex interplay of genetic factors, the airway epithelium, and dysregulation of the immune response. Prostaglandin D2 (PGD2) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as TH2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD2 mainly exerts its biological functions via two G-protein-coupled receptors, the PGD2 receptor 1 (DP1) and 2 (DP2). The DP2 receptor is mainly expressed by the key cells involved in type 2 immune responses, including TH2 cells, type 2 innate lymphoid cells and eosinophils. The DP2 receptor pathway is a novel and important therapeutic target for asthma, because increased PGD2 production induces significant inflammatory cell chemotaxis and degranulation via its interaction with the DP2 receptor. This interaction has serious consequences in the pulmonary milieu, including the release of pro-inflammatory cytokines and harmful cationic proteases, leading to tissue remodelling, mucus production, structural damage, and compromised lung function. This review will discuss the importance of the DP2 receptor pathway and the current understanding of its role in asthma