Novel concepts in virally induced asthma

Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness

Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6,578 Women

While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5×10−8), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1×10−29) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes

Correlation between Bcl-2 and Bax in atrophic and hypertrophic type of actinic keratosis

BACKGROUND: Recent investigations consider actinic keratosis (AK) as an earliest visible pattern of squamous cell carcinoma (SCC). We have analysed the expression of apoptosis-related proteins TP53, Bcl-2 and Bax in 30 atrophic and 30 hypertrophic AK cases. ----- MATERIAL AND METHODS: Immunohistochemical analysis was performed following microwave streptavidin immunoperoxidase protocol on DAKO TechMate Horizon automated immunostainer (DAKO, Copenhagen, Denmark). Monoclonal antibody for TP53 and Bcl-2 and polyclonal antibody for Bax (DAKO, Copenhagen, Denmark) were used. ----- RESULTS: Expression of TP53 showed no significant differences between two analysed groups (chi2-test, P = 0.35636) whereas expression of Bcl-2 and Bax protein was significantly higher in atrophic compared to hypertrophic AK (chi2-test, P = 0.01458 and P = 0.00358, respectively). Comparison of Bcl-2 : Bax ratio in two analysed AK showed significantly higher value in hypertrophic compared to atrophic AK (Mann-Whitney U test, P = 0.02272). Statistical analysis did not show any correlation between patient's sex and age, localization and size of the lesion with expression of investigated oncoproteins (anova, P > 0.05). ----- CONCLUSIONS: Our results may indicate higher resistance of keratinocytes on apoptotic stimuli in hypertrophic compared to atrophic AK. Thus, we suppose that keratinocytes in hypertrophic AK live longer and probably have higher propensity for additional mutations and conversion to overt SCC

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut.

Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis