Lymphoid Follicle Spatial Transcriptomics Resolve an Emphysema-Specific B Cell Signature in COPD

Using Geomx's Digital Space Profiling method for WTA RNA transcriptomics in lung tertiary lymphoid structures (TLS, follicles), we assessed paraffin-embedded and OCT-embedded lung sections from 48 patients, which were classified as Never Smoker Controls (NSC, n=8), Smoker Controls (SC, n=13), and COPD GOLD1-4 patients (n=27 patients). we identified 19 patients with tertiary lymphoid structures (TLS), distributed as 13 COPD patients and 6 SC subjects, with 115 TLS data used for the final data analysis. Overall design: After consenting, lung samples were collected from Smoker Controls (defined pack years >10), and COPD GOLD1-4 patients (defined according to spirometry results). Samples: Pathologist assessed lung samples were obtained from patients undergoing lung biopsy for non-cancer causes or because they needed to receive a lung transplant (COPD stage 4 patients). Lungs were either fresh fixed in OCT fixative and kept at -80C, or, they were fixed in formalin for 24 hours and subsequently embedded in paraffin. ROIs were collected from CD45 labeled lyphoid follices from COPD patients and from smoker control patients.