Maternal asthma and microRNA regulation of soluble HLA-G in the airway

Abstract

Background We previously reported an interaction between maternal asthma and the child’s HLA-G genotype on the child’s subsequent risk for asthma. The implicated SNP at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect may be mediated by these miRs Objective The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. Methods We measured soluble (s)HLA-G concentrations in bronchial alveolar lavage (BAL) fluid (N=36) and plasma (N=57) from adult asthmatics with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, -148b, and -152) transcript levels in airway epithelial cells from the same individuals. Results miR-148b levels were significantly elevated in airway epithelial cells from asthmatics with an asthmatic mother compared to asthmatics without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in BAL fluid among asthmatic individuals with an asthmatic mother but not among those with a non-asthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). Conclusion These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family, and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject’s mother and the subject’s genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of her children persist into adulthood.

Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma

“…Our previous studies (3,5,9) demonstrated associations between HLA-G genetic variation and sHLA-G expression levels in AECs from individuals with asthma. Here we show for the first time that sHLA-G concentrations in the airway are inversely correlated with markers of airway inflammation: asthmatic subjects, regardless of disease severity, with higher concentrations of sHLA-G had lower levels of BAL eosinophils and lower FeNO, both consistent with the Th2-low endotype in asthma.…”

DNA methylation in lung cells is associated with asthma endotypes and genetic risk

“…One hundred twenty-three adult subjects (76 with asthma, 47 without asthma) underwent bronchoscopy between March 2010 and March 2014 at the University of Chicago. Endobronchial brushings were obtained during bronchoscopy, as previously described (37). The asthmatic subjects had a current doctor's diagnosis of asthma, no conflicting pulmonary diagnoses, and were using asthma medications.…”

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

“…Our asthma clinical research program has been collecting lower airway samples from both carefully characterized asthma patients and from control subjects [18, 19]. To overcome previous sampling inconsistencies, we decided to elucidate and model the variability in the microbiome of different lung regions; specifically, the bronchial (endobronchial brushing, EB) and small (bronchoalveolar lavage, BAL) airways.…”