ß-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area.

BACKGROUND: Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors. OBJECTIVE: We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort. METHODS: A total of 588 individuals with moderate-severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC112 ® and Allergy Explorer-ALEX® microarray analysis. RESULTS: The olive tree pollen ß-1,3-glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper-reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross-reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross-reactive carbohydrate determinants (CCDs) IgE was found in about one-third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient-reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity. CONCLUSION AND CLINICAL RELEVANCE: Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns.

Aedes communis Reactivity Is Associated with Bee Venom Hypersensitivity: An in vitro and in vivo Study.

Mosquito bite is usually followed by a local reaction, but severe or systemic reaction may, in rare cases, occur. Allergic reactions to Aedes communis (Ac) may be underestimated due to the lack of reliable diagnostic tools. In this multicenter study, 205 individuals reporting large local reactions to Ac were enrolled and studied for cutaneous or IgE reactivity to Ac, Blattella germanica, Penaeus monodon, and Dermatophagoides pteronyssinus. Extract and molecular IgE reactivity to bees, wasps, hornets, and yellow jacket venoms were also studied in 119 patients with a clinical history of adverse reaction to Hymenoptera. Immunoblot (IB) analysis and immunoCAP IgE inhibition experiments were carried out in selected sera. Ac sensitization was recorded in 96 (46.8%) patients on SPT. Strict relationship between Ac and D. pteronyssinus, B. germanica, P. monodon, or Apis mellifera reactivity on SPT was observed. Ac IgE recognition was seen in 60/131 (45.8%) patients, 49 (81.6%) of them SPT positive, and 5/14 IB reactors. Ac IgE sensitization was associated with Tabanus spp, A. mellifera, Vespula vulgaris, and Polistes dominula reactivity. A strict relationship between Ac IgE reactivity and Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was recorded. IgE reactivity to AC was inhibited in 9/15 cases after serum absorption with the A. mellifera extract. Both SPT and IgE Ac reactivity is observed in about half of patients with a history of large local reactions to mosquito bites. The significant relationship between Ac sensitization and either extract or single bee venom components is suggestive of a "bee-mosquito syndrome" occurrence.

Molecular Recognition Profiles and Clinical Patterns of PR-10 Sensitization in a Birch-Free Mediterranean Area.

BACKGROUND: The order Fagales represents an important cause of tree-pollen allergy in northern countries. We investigated the IgE recognition profiles, mutual relationships, and association with clinical symptoms of a panel of allergens belonging to the PR-10 family, the main proteins responsible for Fagales allergy (Act d 8, Aln g 1, Api g 1, Ara h 8, Bet v 1, Cor a 1.0101, Cor a 1.0401, Gly m 4, Mal d 1, and Pru p 1). METHODS: A total of 526 PR-10-reactive subjects living in central and southern Italy were studied by ImmunoCAP-ISAC-112 microarray analysis. RESULTS: Overall, Bet v 1 reactivity was the most commonly (74%) observed among PR-10 proteins, but Cor a 1.0101 was the most prevalent in participants aged <6 years, and between 15 and 65 years. Overall, 26% of the PR-10-reactive persons were Bet v 1 negative, whilst 93.6% of the PR-10 polyreactive individuals were Bet v 1 positive. Among the 10 PR-10s evaluated, 100 combinations were recorded. The strongest association was observed between molecules with the highest sequence identities (Bet v 1 and Cor a 1.0101, Cor a 1.0401 or Aln g 1; Mal d 1 and Pru p 1). Bet v 1-, Cor a 1.0101-, and Aln g 1-specific IgE recognition was associated with respiratory symptoms, whilst Ara h 8, Cor a 1.0401, Gly m 4, Mal d 1, and Pru p 1 were selectively linked to an oral allergic syndrome. CONCLUSIONS: Testing IgE reactivity to a panel of PR-10s in a birch-free area discloses peculiar relationships between clinical phenotypes and sensitization profiles, allowing the identification of novel cluster patterns.

Delayed allergic reaction to suxamethonium driven by oligoclonal Th1-skewed CD4+CCR4+IFN-gamma+ memory T cells.

BACKGROUND: Muscle relaxants represent the drugs most frequently involved in intraoperative anaphylaxis during surgical procedures. Our aim was to report the case of a delayed reaction to suxamethonium and analyze specific T cell lines with regard to their specificity, phenotype and cytokine profile. METHODS: We generated a drug-specific T cell line from a biopsy at the site of positive intradermal reactions and analyzed the immunophenotype, T cell receptor Vbeta domain expression and cytokine profile. RESULTS: T cells isolated from positive intradermal test reactions to suxamethonium showed a strict dose-dependent proliferation in response to drug-pulsed autologous antigen-presenting cells. The drug-specific CD4+ T cells were oligoclonal memory CD3+CD4+ T cells and expressed the skin homing receptors cutaneous lymphocyte antigen (CLA) and CCR4. Furthermore CD4+ suxamethonium-reactive T cell lines were IFN-gamma-positive and synthesized high levels of IFN-gamma and TNF-alpha. CONCLUSION: The study describes a delayed hypersensitivity to suxamethonium, driven by an oligoclonal T helper cell 1-skewed CD4+ memory T cell population, expressing the skin homing receptors CLA and CCR4.