Regulatory Myeloid-Cell Dynamics In Asthmatics During Pregnancy

Asthma is one of the most common chronic inflammatory lung diseases among pregnant women. Acute asthma exacerbations during pregnancy negatively impact pregnancy outcomes. As myeloid-derived suppressor cell (MDSC) populations are known regulators of airway inflammation and are important in maternal-fetal tolerance, we investigated if percentages of circulating MDSC subsets correlated with clinical indicators of airway inflammation and maternal-fetal tolerance in a cohort of healthy pregnant (HP), asthmatic pregnant (AP) and well controlled asthmatic pregnant (WCAP) women recruited to the B-WELL Mom study. Reciprocal dynamics of circulating MDSC subsets, with granulocytic MDSCs (Gr-MDSCs) increasing over early pregnancy and declining in late stage pregnancy and the reverse trend with monocytic MDSCs (Mo-MDSCs) were identified; the decline of Mo-MDSCs at Visit 3 of pregnancy was higher in AP/WCAP compared to HP whereas the decline of Gr-MDSCs at late stage pregnancy was lower in AP/WCAP compared to HP. In AP/WCAP, positive correlations were observed between both MDSC subsets during pregnancy and Gr-MDSCs correlated positively with fractional exhaled nitric oxide, a surrogate measure of airway inflammation, during early pregnancy; these relations were not identified in HP subjects. Interestingly, soluble HLA-G as well as indoleamine 2,3 dioxygenase activity, both important in maternal-fetal tolerance, showed positive correlations with MDSCs only in HP and not in AP/WCAP subjects. Our studies suggest that differential myeloid-cell dynamics may serve as biomarkers of maternal-fetal tolerance in AP/WCAP subjects.