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.
Rationale:
Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.
Objective:
To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and COPD patients with varying degrees of emphysema.
Methods:
Lung sections from 40 COPD patients and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin and OCT-fixed lung samples obtained from biopsies or lung explants, were assessed for LF presence. Emphysema measurements were obtained from clinical chest CT scans. High confidence transcriptional (HCT) target intersection analyses were conducted to resolve emphysema-induced transcriptional networks.
Measurements And Main Results:
Overall, 115 LFs from ever-smokers and 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 markers genes in subjects with severe emphysema. HCT analysis revealed activation of abnormal B cell activity signature in LFs (q-value: 2.56E-111). LFs from GOLD 1-2 COPD patients with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from GOLD 1-2 COPD patients without emphysema showed an anti-inflammatory 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 towards chronic B cell activation.
Conclusions:
An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis.
More Related Videos
10:37Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
Published on: January 16, 2015
10:39Advanced Imaging of Lung Homing Human Lymphocytes in an Experimental In Vivo Model of Allergic Inflammation Based on Light-sheet Microscopy
Published on: April 16, 2019
Related Concept Videos
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
01:20COPD: Pathogenesis and Clinical Features
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
01:27Chronic Obstructive Pulmonary Disease-IV: Assessement and Diagnostic Studies
Medical History
01:22Chronic Obstructive Pulmonary Disease
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...