Analysis of polymorphisms in olive pollen allergy: IL13, IL4RA, IL5 and ADRB2 genes.

BACKGROUND: Previous results demonstrated that sensitization to specific olive pollen allergens could be related with a different clinical pattern (asthma and/or rhinitis), and that specific patterns of sensitization are regulated by different HLA class II antigens. The authors analyze the possible implication of 7 genetic polymorphisms described as asthma susceptibility genes: IL13 (C-1112T and R130Q), IL4RA (I50V, Q551R), IL5 (C-746T) and ADRB2 (Q27E and R16G) in specific olive pollen allergic sensitization. METHODS: The authors genotyped seven polymorphisms of the IL13, IL4RA, IL5 and ADRB2 genes in 146 patients allergic to olive pollen with seasonal rhinitis/asthma and 50 controls using the polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction techniques. RESULTS: Two polymorphisms of IL13 were associated with allergy to olive pollen: the TT genotype of IL13 C-1112T was decreased (odds ratio, OR = 0.35, p = 0.006) whereas the RQ heterozygous genotype of IL13 R130Q increased in patients allergic to olive pollen (OR = 3.12, p = 0.009). The combined analysis of two IL4RA single nucleotide polymorphisms (SNPs) (I50V and Q551R) showed an association with asthma: IL4RA V50/Q551 was associated with risk (OR = 2.48, p = 0.007) whereas the IL4RA V50R551 haplotype was associated with protection (OR = 0.31, p = 0.003). CONCLUSIONS: The IL13 polymorphisms under study were associated with specific allergy to olive pollen: the IL13 C-1112T polymorphism as a protective factor and the IL13 R130Q polymorphism as a risk factor. Interestingly, although single polymorphisms of IL4RA are not associated with any phenotype analyzed, the interaction between IL4RA I50V/Q551R was strongly associated with the asthma phenotype. IL13 and IL4RA could be relevant markers for allergy to olive pollen and asthma development.

Inhibition of chronic airway inflammation and remodeling by galectin-3 gene therapy in a murine model.

We previously demonstrated that treatment of acute asthmatic rats with gene therapy using plasmid-encoding Galectin-3 (Gal-3) resulted in an improvement of cellular and functional respiratory parameters. The next question that we wanted to clarify was if in a chronic situation where the treated animal continues to inhale the Ag, does this procedure prevent the chronicity and the remodeling? Chronic inflammation was induced by intranasal administration of OVA over a period of 12 wk. In the treated group, the Gal-3 gene was introduced by intranasal instillation in 50 mul of plasmid-encoding Gal-3. Noninvasive airway responsiveness to methacholine was tested at different times. Cells were obtained by bronchoalveolar lavage and used for RNA extraction and cytometric studies. Eosinophils were counted in blood and bronchoalveolar lavage fluid. Real-time PCR was used to measure Gal-3 and cytokine mRNA expression in lung. Lungs were paraffined and histologic analyses were performed (H&E, periodic acid-Schiff, and Masson Trichrome stain). Our results showed that 12 wk after the first intranasal Ag instillation in chronically asthmatic mice, treatment with the Gal-3 gene led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion and subepithelial fibrosis in the chronically asthmatic mice, with a quantitatively measured reduction in lung collagen, a prominent feature of airway remodeling. Plasmid-encoding Gal-3 acts as a novel treatment for chronic asthma in mice producing nearly complete blockade of Ag responses with respect to eosinophil airway accumulation, airway hyperresponsiveness, and remodeling.