Genetic variations in toll-like receptor pathway genes influence asthma and atopy.

Innate immunity is a pivotal defence system of higher organisms. Based on a limited number of receptors, it is capable of recognizing pathogens and to initiate immune responses. Major components of these innate immunity pathogen recognition receptors are the toll-like receptors (TLRs), a family of 11 in humans. They are all membrane bound and through dimerization and complex downstream signaling, TLRs elicit a variety of specific and profound effects. In recent years, the role of TLRs signaling was not only investigated in infection and inflammation but also in allergy. Fuelled by the hygiene hypothesis, which suggests that allergies develop because of a change in microbial exposure and associated immune signals early in life, it had been speculated that alterations in TLRs signaling could influence allergy development. Thus, TLR genes, genetic variations of these genes, and their association with asthma and other atopic diseases were investigated in recent years. This review provides an overview of TLR genetics in allergic diseases.

[Prognosis and treatment of Vernal keratoconjunctivitis in pediatric age: pilot study on 197 patients]. / Prognosi e trattamento della cheratocongiuntivite Vernal in età pediatricia: studio pilota su 197 pazienti.

AIM: Corticosteroids and high-concentrated cyclosporine eyedrops have been used for treatment of severe vernal keratoconjunctivitis (VKC) cases. The purpose of our study was to verify the efficacy of 1% topical cyclosporine in improving severe form of VKC in childhood and investigate for factors affecting the response to therapy. METHODS: We conducted an open trial involving 197 children with severe VKC, who received topical cyclosporine 1% for four months. Ocular subjective symptoms and objective signs were scored in all children at entry, two weeks and four months. Skin prick tests and microscope endothelial cells evaluation were also performed; serum IgE and cyclosporine levels were assessed. RESULTS: The mean score values for severity of subjective symptoms and objective signs were significantly decreased after 2 weeks, and 4 months, compared with those at entry (P<0.001) in all children. Cyclosporine serum levels were not detectable at the end of therapy, nor were endothelial corneal cells damaged. Patients who started the therapy at the beginning of the disease and/or received long-term regimen of treatment with cyclosporine had a faster improvement of ocular signs and symptoms, compared to all other patients. CONCLUSION: Our findings suggest that 1% cyclosporine concentration administrated topically at the beginning of the disease and for a long-term period might be the most effective treatment to control symptoms and local inflammation in severe forms of VKC in childhood.

Prevalence of atopic symptoms among blood donor carriers of mannose-binding lectin variant alleles.

Mannose-binding lectin (MBL) is a C-type soluble collectin involved in the innate immune response. Carriers of MBL gene variant alleles (MBLva) have decreased plasma concentrations of MBL and increased susceptibility to bacterial and viral infections. The aim of the present study is to test the hypothesis that carriers of MBLva could have a different frequency of atopic symptoms as compared to wild-type carriers. A total of 385 consecutively enrolled Caucasian blood donors were studied. Blood specimens underwent genomic analysis and genotyping for MBLva by polymerase chain reaction (PCR). MBLva carrier status was associated with a reduced frequency of allergic rhinitis (OR 0.41 [95% CI 0.2 to 0.8], chi2 = 6.98, p =.008). No relationship was found between MBLva carrier status and asthma or atopic skin symptoms. MBLva might be one of the host-related genetic factors involved in atopic disorders, namely allergic rhinitis.

Association of beta-defensin-1 gene polymorphisms with Pseudomonas aeruginosa airway colonization in cystic fibrosis.

Lung disease and Pseudomonas aeruginosa (P. aeruginosa) airway colonization represent a major cause of morbidity and mortality in cystic fibrosis (CF). Human beta-defensin (hBD)-1 is believed to play an important role in mucosal innate immunity in the lung. This study aimed to investigate whether three single-nucleotide polymorphisms (SNPs) in the 5'-untranslated region of DEFB1, G-52A, C-44G and G-20A were associated with P. aeruginosa airway colonization in CF. A total of 224 CF patients and 196 control subjects were studied. DEFB1 SNPs were characterized by restriction fragment length polymorphisms. Patients' sputum samples were collected and analyzed by standard methods. Single SNP analysis suggested that CF patients carrying the -52AA and the -20GG genotypes had a higher rate of P. aeruginosa airway colonization than patients homozygous and heterozygous for the -52G and -20A alleles (P=0.01 and P=0.007, respectively). A significant association between the ACG haplotype and chronic P. aeruginosa infection was also identified (odds ratio (95% confidence interval): 3.00 (1.42-6.36), P=0.004). These results indicate that variant alleles in DEFB1 might contribute to the colonization of P. aeruginosa in CF.