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- Title
Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease.
- Authors
Rojas-Quintero, Joselyn; Ochsner, Scott A.; New, Felicia; Divakar, Prajan; Chen Xi Yang; Wu, Tianshi David; Robinson, Jerid; Chandrashekar, Darshan Shimoga; Banovich, Nicholas E.; Rosas, Ivan O.; Sauler, Maor; Kheradmand, Farrah; Gaggar, Amit; Margaroli, Camilla; Estepar, Raul San Jose; McKenna, Neil J.; Polverino, Francesca
- 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 eversmokers 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 eversmokers andGlobal Initiative for ChronicObstructive LungDisease (GOLD) 1-2 andGOLD3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cellmarker 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 frompatients withGOLD 1-2 COPDwith emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs frompatients with GOLD1-2COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cellmaturation 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.
- Subjects
CHRONIC obstructive pulmonary disease; B cells; TRANSCRIPTOMES; GENE regulatory networks; GENE expression
- Publication
American Journal of Respiratory & Critical Care Medicine, 2024, Vol 209, Issue 1, p48
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202303-0507LE