Genetics of allergy and allergic sensitization: common variants, rare mutations

Abstract

Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T-cell differentiation, TGFβ signaling, regulatory T-cell function and skin/mucosal function as well as yet unknown mechanisms associated with newly identified genes. Future studies, in combination with data on gene expression and epigenetics, are expected to increase our understanding of the pathogenesis of allergy.

A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

“…Unlike the CMC observed in patients and our findings for IL-17, the pathogenesis of severe allergy and hyper-IgE in these patients is more difficult to decipher, as monogenic causes of isolated allergy and hyper-IgE affecting specific cytokine signaling pathways are only just beginning to emerge (51, 52). However, the microarray analysis of CD4 + T cells was instructive, revealing aberrant expression of potential mediators of inflammation in ZNF341-deficient patients (Fig.…”

Are dust mite allergens more abundant and/or more stable than other Dermatophagoides pteronyssinus proteins?

“…Other influences on sensitization include additional environmental exposures, adjuvants (natural 6 and anthropogenic 7 ), genetic susceptibility, 8 and a modern hygienic lifestyle. 9 A limitation of this protocol is that these studies were performed with whole mite extract in order to sample the maximum number of RNA transcripts and proteins for stability assays.…”

Proteases of Dermatophagoides pteronyssinus

“…Examples include genetic susceptibility [37], the modern hygienic lifestyle [38], as well as natural and anthropogenic adjuvants [39,40]. Protease activity is likely one of many factors that can skew the immune response towards allergy.…”