The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex

Gary M Hunninghake,Sunita S Sharma,Amy Murphy,Vincent J Carey,Angela J Rogers,Jen-Hwa Chu,Michael H Cho,Benjamin A Raby,Blanca E Himes

doi:10.1186/1471-2466-11-17

Abstract

BackgroundThe relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex specifically) are not known.MethodsPeripheral blood CD4+ T cells from 223 participants from the Childhood Asthma Management Program (CAMP) with simultaneous measurement of IgE. Total RNA was isolated, and expression profiles were generated with Illumina HumanRef8 v2 BeadChip arrays. Modeling of the relationship between genome-wide gene transcript levels and IgE levels was performed in all subjects, and stratified by sex.ResultsAmong all subjects, significant evidence for association between gene transcript abundance and IgE was identified for a single gene, the interleukin 17 receptor B (IL17RB), explaining 12% of the variance (r2) in IgE measurement (p value = 7 × 10-7, 9 × 10-3 after adjustment for multiple testing). Sex stratified analyses revealed that the correlation between IL17RB and IgE was restricted to males only (r2 = 0.19, p value = 8 × 10-8; test for sex-interaction p < 0.05). Significant correlation between gene transcript abundance and IgE level was not found in females. Additionally we demonstrated substantial sex-specific differences in IgE when considering multi-gene models, and in canonical pathway analyses of IgE level.ConclusionsOur results indicate that IL17RB may be the only gene expressed in CD4+ T cells whose transcript measurement is correlated with the variation in IgE level in asthmatics. These results provide further evidence sex may play a role in the genomic regulation of IgE.

Highlights

The relationships between total serum immunoglobulin E (IgE) levels and gene expression patterns in peripheral blood CD4+ T cells are not known
Evidence for sexually-distinct genetic determinants of IgE has been demonstrated in genome-wide linkage analyses of IgE in some, [7] but not all studies [8]. Based on these findings we hypothesized that genomewide CD4+ T cell microarray analyses would provide unique insights into genes that correlate with the variability in IgE level, and that sex would be an important modifier of these correlations. To test these hypotheses we explored the relationship between total serum IgE levels and genome-wide gene expression transcript abundance in a cohort of 223 young adults with asthma, both in all subjects and within each sex
Single Gene Regressive Strategies Significant evidence for association between transcript abundance and total serum IgE was identified for a single gene, interleukin 17 receptor B (IL17RB), explaining

Summary

Introduction

The relationships between total serum IgE levels and gene expression patterns in peripheral blood CD4+ T cells (in all subjects and within each sex ) are not known. Total serum immunoglobulin E (IgE) is a risk factor for both the development of [1] and disease severity in asthma [2]. The production of IgE is controlled by a complex regulatory process that involves isotype class switching by mononuclear B lymphocytes, [3] a CD4+ T cell dependent process [3]. To our knowledge, there has been no analysis of the correlation between genome-wide CD4+ T cell gene expression and the variability in serum IgE among asthmatics. Sex-related differences in IgE are present early in life [5] and persist into adulthood [6].

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