Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.

Background: Polymerized allergoids coupled to nonoxidized mannan (PM‐allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM‐allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM‐allergoids administered sublingually in comparison with native allergens.Methods: Three immunization protocols (4‐8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.Results: A quick antibody response and higher IgG2a/IgE ratio were observed with PM‐allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL‐4 ratio with a quick IL‐10 production by submandibular LN cells. An increase in CD4⁺CD25^highFOXP3⁺ Treg cells was detected in LNs and spleen of mice treated with PM‐allergoids. These allergoids were better captured than native allergens by antigen‐presenting (CD45⁺MHC‐II⁺) cells obtained from the sublingual mucosa, including DCs (CD11b⁺) and macrophages (CD64⁺). Importantly, all the differential effects induced by PM‐allergoids were abolished when using oxidized instead of nonoxidized PM‐allergoids.Conclusion: Our results demonstrate for the first time that PM‐allergoids administered through the sublingual route promote the generation of Th1 and FOXP3⁺ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen‐presenting cells.

Background: Polymerized allergoids conjugated to mannan (PM) are suitable vaccines for allergen‐specific immunotherapy (AIT). Alum remains the most widely used adjuvant in AIT, but its way of action is not completely elucidated. The better understanding of the mechanisms underlying alum adjuvanticity could help to improve AIT vaccine formulations.Objective: We sought to investigate the potential influence of alum in the tolerogenic properties imprinted by PM at the molecular level.Methods: Flow cytometry, ELISAs, cocultures, intracellular staining and suppression assays were performed to assess alum and PM effects in human dendritic cells (DCs). BALB/c mice were immunized with PM alone or adsorbed to alum. Allergen‐specific antibodies, splenocyte cytokine production and splenic forkhead box P3 (FOXP3)⁺ regulatory T (Treg) cells were quantified. Metabolic and immune pathways were also studied in human DCs.Results: Alum decreases PD‐L1 expression and IL‐10 production induced by PM in human DCs and increases pro‐inflammatory cytokine production. Alum impairs PM‐induced functional FOXP3⁺ Treg cells and promotes Th1/Th2/Th17 responses. Subcutaneous immunization of mice with PM plus alum inhibits in vivo induction of Treg cells promoted by PM without altering the capacity to induce functional allergen‐specific blocking antibodies. Alum inhibits mTOR activation and alters metabolic reprogramming by shifting glycolytic pathways and inhibiting reactive oxygen species (ROS) production in PM‐activated DCs, impairing their capacity to generate functional Treg cells.Conclusion: We uncover novel mechanisms by which alum impairs the tolerogenic properties induced by PM, which might well contribute to improve the formulation of novel vaccines for AIT.

In recent years, the allergological importance of different mite species not belonging to the family Pyroglyphidae has been demonstrated. These mites, commonly named storage mites, include Lepidoglyphus destructor, Glycyphagus domesticus, Tyrophagus putrescentiae, Acarus siro, Aleuroglyphus ovatus, Suidasia medanensis and Thyreophagus entomophagus. Several allergens from these species have been purified, sequenced and cloned. Many of these allergens have shown sequence homology and a biological function similar to those previously described in Blomia tropicalis and the Dermatophagoides spp. The main allergens described in storage mites include fatty acid binding proteins, tropomysin and paramyosin homologues, apoliphorine like proteins, alfa-tubulines and other, such as group 2, 5 and 7 allergens, which definitive biological function has not been described yet. Besides the purification and characterization of allergens, the allergenicity of other species such as Acarus farris, Austroglycyphagus malaysiensis, Blomia kulagini and B. tjibodas, Cheyletus eruditus, Chortoglyphus arcuatus, Gohieria fusca, Thyreophagus entomophagus and Tyrophagus longior has been investigated. Research has also been conducted to identify allergens in parasitic mites, such as Psoroptes ovis, Sarcoptes scabiei, Varroa jacobsoni, Diplaegidia columbae and Hemisarcoptes cooremani. The allergenicity of mites present in agricultural environments has been investigated. Crossreactivity studies have also been performed to elucidate to what extent all these mites share common, or species specific epitopes. Herein we present a comprehensive review of the allergenicity of mite species which have been implicated in human respiratory and/or dermatological diseases.

Grasses and olive trees are the most common sources of allergenic pollen worldwide. Although they share some allergens, there are few studies analyzing the in vitro cross-reactivity between them. The aim was to define the cross-reactivity between Olea europaea and Phleum pratense using well-characterized sera of allergic children from Madrid, Spain. 66 patients (mean age 10.32+/−4.07 years) were included in the study. All suffered from rhinoconjuntivitis and/or asthma and had a positive skin test and/or specific IgE determination to olive and grass pollen. Serum sIgE to individual allergens was conducted and sIgE against different grass species and olive was also determined by ELISA. Inhibition assays were performed using two serum sources, containing, or not, sIgE to minor allergens. Mass spectrometry analysis was performed in both extracts. 59/66 (89.39%) children had a positive sIgE determination by ELISA to grasses and 57/66 (86.36%) to olive pollen. There was no significant correlation between sIgE levels to grass and olive. Inhibition assays demonstrated no cross-reactivity between P. pratense and olive pollen when using the pool containing mainly sIgE to major allergens, whereas minimal to moderate cross-reactivity was detected when the serum contained high sIgE titers to minor allergens. Proteomic analyses revealed the presence of 42 common proteins in grasses and olive pollens. No in vitro cross-reactivity was observed when sIgE was mainly directed to major allergens. In our population, sensitization to olive and grasses is not due to cross-reactivity. The contribution of the major allergens seems to be determinant.