Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease

肺病 医学 病理 肺气肿 疾病 转录组 毛囊 基因表达 内科学 基因 生物 遗传学
作者
Joselyn Rojas,Scott A. Ochsner,Felicia New,Prajan Divakar,Chen Xi Yang,Tianshi David Wu,Jerid W. Robinson,Darshan S. Chandrashekar,Nicholas E. Banovich,Iván O. Rosas,Maor Sauler,Farrah Kheradmand,Amit Gaggar,Camilla Margaroli,Raúl San Jośe Estépar,Neil J. McKenna,Francesca Polverino
出处
期刊:American Journal of Respiratory and Critical Care Medicine [American Thoracic Society]
卷期号:209 (1): 48-58 被引量:4
标识
DOI:10.1164/rccm.202303-0507le
摘要

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.
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