Spatial Transcriptomics Resolve an Emphysema-specific Lymphoid Follicle B Cell Signature in COPD
Joselyn Rojas-Quintero1, Scott A Ochsner2, Felicia New3
1Baylor College of Medicine Department of Medicine, 171841, Pulmonary, Critical Care and Sleep Medicine, Houston, Texas, United States.
Chronic obstructive pulmonary disease (COPD) involves B cells in emphysema. This study found abnormal B cell activation in lymphoid follicles (LFs) in emphysema patients, suggesting a role in autoimmune pathogenesis.
Area of Science:
- Immunology
- Pulmonology
- Genomics
Background:
- Chronic obstructive pulmonary disease (COPD) features a significant, yet not fully understood, B cell immune component in emphysema.
- Lymphoid follicles (LFs) are key sites of B cell activity.
Purpose of the Study:
- To investigate the transcriptomic profiles of lymphoid follicles (LFs) in individuals who smoke but do not have COPD, and in COPD patients with varying degrees of emphysema.
- To elucidate the role of B cells in the pathogenesis of emphysema.
Main Methods:
- Spatial proteomic and transcriptomic profiling of 115 lymphoid follicles (LFs) from 40 COPD patients and ever-smokers.
- Analysis of lung sections using formalin and OCT fixation, with emphysema severity assessed by chest CT scans.
- High-confidence transcriptional (HCT) target intersection and protein-RNA network analyses to identify emphysema-associated transcriptional networks.
Main Results:
- No lymphoid follicles (LFs) were observed in never-smokers.
- Significantly elevated expression of B cell markers and LF assembly genes in severe emphysema.
- Abnormal B cell activation signature identified in LFs from COPD patients with emphysema (q-value: 2.56E-111).
- LFs in emphysema exhibit a unique signature indicative of chronic B cell activation, associated with antigen presentation, inflammation, B cell maturation, and antibody production.
Conclusions:
- Off-targeted B cell activation within lymphoid follicles (LFs) is linked to the autoimmune-mediated pathogenesis of emphysema.
- These findings highlight a specific B cell-driven pathway in emphysema development.
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