Jarrett Morrow, PhD

Channing Division of Network Medicine
Jarrett D. Morrow *, Peter J. Castaldi, Adel Boueiz, Robert P. Chase, Jeong H. Yun, Edwin K. Silverman, Craig P. Hersh
Lung B cell gene expression signature of emphysema in peripheral blood

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction accompanied by chronic inflammation and emphysematous destruction. We previously identified a COPD-associated network module of co-expressed genes in lung tissue enriched for B cell pathways. We sought to better understand the transcriptomic B cell signature of emphysema in peripheral blood using this lung module.

Methods: Using blood RNA-sequencing data from the COPDGene study, we created an expression score for the genes from the COPD-associated network module. We tested association between both percent emphysema and COPD status and the expression score. To account for variation in B cell abundance, we included blood cell proportions in the models, calculated using computational deconvolution with single cell RNA sequencing reference data.

Results: Among the 3,985 subjects with RNA-seq data, 1,601 had COPD and 1,609 were controls. We observed an association between the expression score and both percent emphysema (p-value = 0.002) and COPD status (p-value = 0.04), recapitulating the COPD lung finding in peripheral blood. The score was lower in more severe emphysema and lower in COPD. In our previous lung tissue study, the expression signature of the module was higher in COPD. Discordant B cell signatures across lung and blood have been previously observed.

Conclusions: We sought to better understand the blood B cell signature of emphysema. We observed associations between both emphysema and COPD status and the B cell module expression score. Our efforts seek to inform personalized treatments and preventative measures for COPD, particularly in regards to early detection.