PD01 - Respiratory allergens in human milk: potential impact on susceptibility to allergic airway disease

Poster discussion presentationInternational audienc

Activation of natural regulatory T cells by IgG Fc-derived peptide Tregitopes

We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+CD25HiFoxP3+ natural regulatory T cells (nTRegs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with TRegs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity

A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

There is currently no approved treatment for primary Sjögren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials

Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

The clinical efficacy of sublingual immunotherapy (SLIT) with natural allergen extracts has been established in IgE-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. Sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. The oral immune system comprises various antigen-presenting cells, including Langerhans cells, as well as myeloid and plasmacytoid dendritic cells (DCs) with a distinct localisation in the mucosa, along the lamina propria and in subepithelial tissues, respectively. In the absence of danger signals, all these DC subsets are tolerogenic in that they support the differentiation of Th1- and IL10-producing regulatory CD4+ T cells. Oral tissues contain limited numbers of mast cells and eosinophils, mostly located in submucosal areas, thereby explaining the good safety profile of SLIT. Resident oral Th1, Th2, and Th17 CD4+ T cells are located along the lamina propria, likely representing a defence mechanism against infectious pathogens. Second-generation sublingual vaccines are being developed, based upon recombinant allergens expressed in a native conformation, possibly formulated with Th1/T reg adjuvants and/or mucoadhesive particulate vector systems specifically designed to target oral dendritic cells

Enhancing sublingual immunotherapy by systemic or local factors: a role for vitamin D and lingual tonsil?

Enhancing sublingual immunotherapy by systemic or local factor

Specific IgE recognition of pollen allergens from subtropic grasses in patients from the subtropics

Background Pollens of subtropical grasses, Bahia (Paspalum notatum), Johnson (Sorghum halepense), and Bermuda (Cynodon dactylon), are common causes of respiratory allergies in subtropical regions worldwide. Objective To evaluate IgE cross-reactivity of grass pollen (GP) found in subtropical and temperate areas. Methods Case and control serum samples from 83 individuals from the subtropical region of Queensland were tested for IgE reactivity with GP extracts by enzyme-linked immunosorbent assay. A randomly sampled subset of 21 serum samples from patients with subtropical GP allergy were examined by ImmunoCAP and cross-inhibition assays. Results Fifty-four patients with allergic rhinitis and GP allergy had higher IgE reactivity with P notatum and C dactylon than with a mixture of 5 temperate GPs. For 90% of 21 GP allergic serum samples, P notatum, S halepense, or C dactylon specific IgE concentrations were higher than temperate GP specific IgE, and GP specific IgE had higher correlations of subtropical GP (r = 0.771-0.950) than temperate GP (r = 0.317-0.677). In most patients (71%-100%), IgE with P notatum, S halepense, or C dactylon GPs was inhibited better by subtropical GP than temperate GP. When the temperate GP mixture achieved 50% inhibition of IgE with subtropical GP, there was a 39- to 67-fold difference in concentrations giving 50% inhibition and significant differences in maximum inhibition for S halepense and P notatum GP relative to temperate GP. Conclusion Patients living in a subtropical region had species specific IgE recognition of subtropical GP. Most GP allergic patients in Queensland would benefit from allergen specific immunotherapy with a standardized content of subtropical GP allergens