Publication Date
1-1-2024
Journal
American Journal of Respiratory and Critical Care Medicine
DOI
10.1164/rccm.202303-0507LE
PMID
37934672
PMCID
PMC10870877
PubMedCentral® Posted Date
12-8-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Pulmonary Emphysema, Proteomics, Pulmonary Disease, Chronic Obstructive, Gene Expression Profiling, Lymphadenopathy, Emphysema, lymphoid follicles, autoimmunity, switch-class recombination, centrilobular emphysema, metabolic reprogramming
Abstract
Rationale
Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.
Objectives
To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.
Methods
Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks.
Measurements and Main Results
Overall, 115 LFs from ever-smokers and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1–2 and GOLD 3–4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell marker genes in subjects with severe emphysema. High-confidence transcriptional analysis revealed activation of an abnormal B cell activity signature in LFs (q-value = 2.56E-111). LFs from patients with GOLD 1–2 COPD with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from patients with GOLD 1–2 COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cell maturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed toward chronic B cell activation.
Conclusions
An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.
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