Divergent transcriptional profiles in pediatric asthma patients of low and high socioeconomic status

Abstract

Aim: There are marked socioeconomic disparities in pediatric asthma control, but the molecular origins of these disparities are not well understood. To fill this gap, we performed genome-wide expression profiling of monocytes and T-helper cells from pediatric asthma patients of lower and higher socioeconomic status (SES).

Method: Ninety-nine children with asthma participated in a cross-sectional assessment. Out of which 87% were atopic, and most had disease of mild (54%) or moderate (29%) severity. Children were from lower-SES (n = 49; household income <$50 000) or higher-SES (n = 50; household income >$140 000) families. Peripheral blood monocytes and T-helper cells were isolated for genome-wide expression profiling of mRNA.

Results: Lower-SES children had worse asthma quality of life relative to higher-SES children, by both their own and their parents' reports. Although the groups had similar disease severity and potential confounds were controlled, their transcriptional profiles differed notably. The monocytes of lower-SES children showed transcriptional indications of up-regulated anti-microbial and pro-inflammatory activity. The T-helper cells of lower-SES children also had comparatively reduced expression of genes encoding γ-interferon and tumor necrosis factor-α, cytokines that orchestrate Type 1 responses. They also showed up-regulated activity of transcription factors that polarize cells towards Type 2 responses and promote Th17 cell maturation.

Conclusion: Collectively, these patterns implicate pro-inflammatory monocytes and Type 2 cytokine activity as mechanisms contributing to worse asthma control among lower-SES children.

Keywords: asthma; cytokines; health disparities; pediatrics.

Figure 1

Pediatric asthma patients reported on multiple dimensions of their asthma quality of life, and so did one of their patents. Across reporters, children from families of lower socioeconomic status (SES) had worse quality of life than counterparts from higher-SES families.

Figure 2

Linear models were used to estimate the magnitude of differential gene expression in groups of pediatric asthma patients with lower versus higher socioeconomic status (SES). The models were adjusted for a panel of a priori selected covariates. Genes showing 1.20-fold differential expression between groups served as input into higher-order bioinformatics analyses using the Transcription Factor Element Listening System. This platform quantified the prevalence of transcription factor binding motifs (TFBMs) in promoters of differentially expressed genes. TFBM ratios >1 indicate specified transcriptional pathway is up-regulated with low SES; ratios <1 indicate converse. Upper panel shows findings on CD14+ monocytes, and lower panel shows findings in CD3+/CD4+ T-helper lymphocytes.