Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

<p>Abstract</p> <p>Background</p> <p>Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked <it>Alternaria </it>sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying <it>Alternaria </it>sensitivity and asthma, in these studies we examined T cell responses to <it>Alternaria </it>antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma.</p> <p>Methods</p> <p>Sixty children with <it>Alternaria</it>-sensitive moderate-severe asthma were compared to 49 children with <it>Alternaria</it>-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in <it>Alternaria</it>-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 <it>Alternaria</it>-specific T-cells, cultures were stimulated in media alone, <it>Alternaria alternata </it>extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells.</p> <p>Results</p> <p>Children with <it>Alternaria</it>-sensitive moderate-severe asthma trended to have increased sensitivities to <it>Cladosporium </it>(46% versus 35%), to <it>Aspergillus </it>(43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to <it>Alternaria</it>-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of <it>Alternaria</it>-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics to <it>Alternaria </it>extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398.</p> <p>Summary</p> <p>In children with <it>Alternaria</it>-sensitive moderate severe asthma, there was an increased Th2 response to <it>Alternaria </it>stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in <it>Alternaria</it>-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.</p

Prevalence of immunoglobulin E for fungi in atopic children

Background The prevalence of sensitization to fungi in young atopic patients in relation to age and clinical importance is largely unknown. Objective The aim of this study was to investigate the prevalence of sensitization to different fungi in atopic children in relation to age and other aeroallergens. Methods A total of 137 atopic children (male 62%, female 38%; mean age 5 years and 9 months, range 5 months-14 years) were studied. Sera of all patients were routinely tested for total IgE and specific IgE against aeroallergens and milk. Positive sera were also tested for IgE against Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum and Penicillium chrysogenum, using the Pharmacia Enzyme CAP procedure. Results In this. study in atopic children total IgE showed a significant linear relation with age, whereas specific IgE against outdoor fungi, indoor fungi and house dust mite showed significant non linearity with age. Prevalence of specific IgE for Cladosporium ranked first, followed closely by Aspergillus and Alternaria. Calculation of the sensitization of indoor and outdoor fungi showed maximum prevalence at 7.8 years, followed by lower values at higher ages. A similar significant relation was also found for Alternaria, while this relation was not significant for the other individual fungi. Specific IgE for indoor a nd outdoor fungi was associated with the presence of specific IgE for aeroallergen and milk. We found that all children aged 4 years and older showed IgE for house dust mite that (lid not decline with increasing age. Conclusions Sensitization to fungi is prevalent in childhood, with an age-dependent distribution reaching maximum values at 7.7-7.8 years, followed by a decline for all fungal sensitization with increasing age. The importance and relative contribution of fungal sensitization to airway disease, compared with the other allergens, remains to be established

Development of Tungsten and Tungsten Alloys for DEMO Divertor Applications via MIM Technology

This paper is an overview of the very first results obtained on pure tungsten (W) and oxide dispersed strengthened (ODS) W alloys produced by the Metal Injection Molding (MIM) technique for fusion applications. An extensive mechanical and physical characterization was performed, together with microstructural material investigation. The reported work was accomplished within the framework of the European Fusion Development Agreement work program. The main objective was to develop suitable tungsten grades for structural and armor divertor applications in the future DEMO fusion reactor

Encapsulation of GFP in Complex Coacervate Core Micelles

Protein encapsulation with polymers has a high potential for drug delivery, enzyme protection and stabilization. Formation of such structures can be achieved by the use of polyelectrolytes to generate so-called complex coacervate core micelles (C3Ms). Here, encapsulation of enhanced green fluorescent protein (EGFP) was investigated using a cationic-neutral diblock copolymer of two different sizes: poly­(2-methyl-vinyl-pyridinium)₄₁-<i>b</i>-poly­(ethylene-oxide)₂₀₅ and poly­(2-methyl-vinyl-pyridinium)₁₂₈-<i>b</i>-poly­(ethylene-oxide)₄₇₇. Dynamic light scattering and fluorescence correlation spectroscopy (FCS) revealed a preferred micellar composition (PMC) with a positive charge composition of 0.65 for both diblock copolymers and micellar hydrodynamic radii of approximately 34 nm. FCS data show that at the PMC, C3Ms are formed above 100 nM EGFP, independent of polymer length. Mixtures of EGFP and nonfluorescent GFP were used to quantify the amount of GFP molecules per C3M, resulting in approximately 450 GFPs encapsulated per micelle. This study shows that FCS can be successfully applied for the characterization of protein-containing C3Ms