Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes

Abstract

SummaryThe 13q33-34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty-four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy.

Human Ascariasis Increases the Allergic Response and Allergic Symptoms

“…Studies in humans and other mammals support the role of genetic factors in the predisposition to Ascaris [37,47] but few genes have been identified so far [43,[48][49][50][51]52•]. A summary of genes and genomic regions associated with the susceptibility to human ascariasis is presented in Table 1.…”

Lack of Association Between LIG4 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

“…According to the inclusion criteria, seven case-control studies Fu et al, 2003;Han et al, 2004;Lee et., al 2005;BCAC, 2006;GarciaClosas et al, 2006;Acevedo et al, 2009;Jakubowska et al, 2010) appeared to have met the inclusion criteria. The flow chart of study selection is shown in Figure 1.…”

The evolution of the Th2 immune responses and its relationships with parasitic diseases and allergy

“…Una característica de estos estudios es que los alelos de propensión a helmintiasis y de respuesta contra alérgenos se han investigado en poblaciones y ambientes diferentes, por lo que las conclusiones son indirectas en su mayoría (62)(63), limitación que se extiende a otras investigaciones sobre el tema que emplean métodos de bioinformática (64). En cambio, en un estudio reciente se observó, en una misma población expuesta a alérgenos de ácaros y A. lumbricoides, asociaciones de algunos alelos con la respuesta IgE contra A. lumbricoides, pero no con la dirigida a los ácaros (65).…”