Table 3.
Cell Type–Specific Gene Expression Associated with Prospective Exacerbation Rates in COPDGene and ECLIPSE
| COPDGene |
ECLIPSE |
Replication Results |
|||||
|---|---|---|---|---|---|---|---|
| Variable Genes in Cell Type– Specific Transcriptome | Cell Type– Specific Genes Associated with Prospective Exacerbation Rates | Variable Genes in Cell Type– Specific Transcriptome | Cell Type– Specific Genes Associated with Prospective Exacerbation Rates | Replicated Cell Type–Specific Genes Associated with Prospective Exacerbation Rates | Replicated Cell Type–Specific Genes Also in the List of 214 Genes Associated with All 3 Exacerbation Phenotypes | ||
| Neutrophils | 12,080 | 62 up, 763 down | 10,804 | 437 up, 324 down | 3 up, 29 down | ↑TLR2 | |
| CD4+ T cells | 10,451 | 192 up, 2,191 down | 5,944 | 115 up, 258 down | 3 up, 38 down | ↓B3GALT2, ↑BTLA, ↓CCR6, ↓ZBTB25 | |
| B cells | 4,188 | 2 up, 2 down | 5,729 | 25 up, 16 down | — | — | |
| NK cells | 3,451 | 113 up, 48 down | 7,645 | 74 up, 31 down | 3 up | — | |
| CD8+ T cells | 2,881 | 28 up, 60 down | 13,139 | 466 up, 1,438 down | 10 down | — | |
| Monocytes | 3,130 | 24 up, 18 down | 4,994 | 5 up | — | — | |
| Dendritic cells | 924 | 13 up, 1 down | 508 | 17 up, 2 down | — | — | |
| Plasma cells | 1,590 | 14 up | 1,342 | — | — | — | |
| Mast cells | 1,793 | — | 1,046 | — | — | — | |
| Eosinophils | 82 | — | 76 | — | — | — | |
Definition of abbreviations: COPDGene = Genetic Epidemiology of COPD; ECLIPSE = Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; NK = natural killer.
Cell-type–specific gene expression of 10 major leukocytes (eosinophils, dendritic cells, mast cells, monocytes, neutrophils, plasma cells, NK cells, CD4+ and CD8+ T cells, and B cells) were queried using CIBERSORTx. The COPDGene count matrix included 25,171 genes, and the ECLIPSE count matrix included 19,526 genes. In testing significant association with prospective exacerbation rate, linear models adjusted for sex, age, race, smoking status, smoking pack-years, FEV1% predicted, exacerbation history, microarray batch ID (only in ECLIPSE), and white blood cell counts.