Transcriptomic age acceleration is associated with plasmablast-related immune remodeling in IgG4-related disease

Abstract Biological aging profoundly influences immune function, yet its role in shaping immune remodeling within chronically inflamed tissues remains unclear. We investigated whether transcriptomic age identifies a plasmablast-associated immune aging pattern in IgG4-related disease (IgG4-RD). To address this question, bulk RNA sequencing was performed on submandibular gland lesions from 49 patients with IgG4-RD and 3 controls. Transcriptomic age (tAge) was estimated using a transcriptome-based aging model, and age acceleration was calculated as the residual from chronological age. Associations between age acceleration, immune transcriptional modules, and clinical characteristics were evaluated using Spearman correlation analyses. Transcriptomic age correlated with chronological age (ρ = 0.473, P< 0.001), whereas age acceleration was associated with serum IgG4 concentrations (ρ = 0.446, P = 0.001). Among immune transcriptional modules, the plasmablast signature showed the strongest positive association with age acceleration (ρ = 0.312, nominal P = 0.029), although this association did not remain significant after correction for multiple comparisons (FDR-adjusted P = 0.304). Germinal center B-cell and activated B-cell programs showed inverse trends. The plasmablast module also correlated with serum IgG4 levels. Together, these exploratory findings suggest a coordinated pattern linking transcriptomic age acceleration, plasmablast enrichment, and enhanced IgG4 responses. Rather than establishing a mechanistic pathway, these findings identify a candidate plasmablast-associated immune aging pattern that warrants validation in independent cohorts.