RT Journal Article
SR Electronic
T1 Systemic Markers of Adaptive and Innate Immunity Are Associated with COPD Severity and Spirometric Disease Progression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 193920
DO 10.1101/193920
A1 Eitan Halper-Stromberg
A1 Jeong H. Yun
A1 Margaret M. Parker
A1 Ruth Tal Singer
A1 Amit Gaggar
A1 Edwin K. Silverman
A1 Sonia Leach
A1 Russell P. Bowler
A1 Peter J. Castaldi
YR 2017
UL http://biorxiv.org/content/early/2017/11/14/193920.abstract
AB The progression of chronic obstructive pulmonary disease (COPD) is associated with marked alterations in circulating immune cell populations, but no studies have characterized alterations in these cell types across the full spectrum of lung function impairment in current and former smokers. In 6,299 subjects from the COPDGene and ECLIPSE studies, we related Coulter blood counts and proportions to cross-sectional FEV1 adjusting for current smoking status. We also related cell count measures to three-year change in FEV1 in ECLIPSE subjects. In a subset of subjects with blood gene expression data, we used cell type deconvolution methods to infer the proportions of immune cell subpopulations, and we related these to COPD clinical status. We observed that FEV1 levels are positively correlated with lymphocytes and negatively correlated with myeloid populations such as neutrophils and monocytes. In multivariate models, absolute cell counts and proportions were associated with cross-sectional FEV1, and lymphocytes, monocytes, and eosinophil counts were predictive of three-year change in lung function. Using cell type deconvolution to study immune cell subpopulations, we observed that subjects with COPD had a lower proportion of CD4+ resting memory cells and naive B cells compared to non-COPD smokers. Alterations in circulating immune cells in COPD support a mixed pattern of lymphocyte suppression and an enhanced myeloid cell immune response. Cell counts and proportions contribute independent information to models predicting lung function suggesting a critical role for immune response in long-term COPD outcomes. Cell type deconvolution is a promising method for immunophenotyping in large cohorts.