Regulatory Myeloid-Cell Dynamics In Asthmatics During Pregnancy

Abstract 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement Research reported in this publication was supported by HHSN275201300014C (awarded to A.S. and J.R.B) and HL128502 awarded to JSD. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by University of Alabama at Birmingham Institutional Review Board (IRB-140321010) and written informed consent was obtained from all participants I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.