B-cell immune repertoire sequencing in tobacco cigarette smoking, vaping, and chronic obstructive pulmonary disease in the COPDGene cohort
Year: 2025
Type: article
Abstract: Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear. Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use. Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at 5% FDR and suggestive associations at 10% FDR. Results: Among 234 non-Hispanic white (NHW) and African American (AA) participants, CS and dual-use were significantly positively associated with increased secretory IgA production, with dual-use showing the strongest associations. Dual-use was positively associated with class switching and B-cell clonal expansion, indicating increased B-cell activation, with similar trends in those only smoking or only vaping. The IGHV5-51*01 allele was increased in dual users. Conclusions: CS and vaping additively enhance B-cell activation, most notably in dual-users. CS and vaping are significantly associated to multiple alterations in B-cell function including increased class switching, clonal expansion, and a shift towards IgA-producing cell populations. These changes could be relevant to response to infection and vaccinations and merit further study.
Source: Frontiers in Immunology
Institutions: Brigham and Women's Hospital, Harvard University, VA Boston Healthcare System, Yale University, Baylor College of Medicine, Colorado School of Public Health, University of Michigan, VA Ann Arbor Healthcare System, Ann Arbor VA Medical Center, University of California San Diego, VA San Diego Healthcare System, University of California, Santa Cruz
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use, Electronic Cigarette Vapor Inhalation Adversely Affects Lung Cellular and Physiologic Function and Alters Systemic Inflammatory Pathways, G528286723, (2 of 2) Genetic Epidemiology of COPD, Using Integrative Genomics To Identify and Characterize Emphysema-Associated eQTL, (1 of 2) Genetic Epidemiology of COPD, Role of MIF and CD74 in the pathogenesis of emphysema, COPD GWAS Functional Variant Identification in Airway Epithelial Cells using Deep Learning Splicing Models, Imaging and multi-omics analyses to identify molecular subtypes of distinct emphysema patterns, Multi-omic Risk Prediction of Chronic Obstructive Pulmonary Disease in European- and African-Ancestry Populations, Genetic variants that affect the airway epithelium to drive obstructive lung disease, Protective effects of metformin against cigarette smoke-induced lung pathologies via regulation of fatty acids metabolism
OpenAlex ID: W4410040716