Exploratory comparison of immune cell compositions across organs in IgG4-related disease

OBJECTIVES: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder affecting multiple organs, but the extent to which immune microenvironments differ across tissues remains unclear. We compared immune cell compositions between submandibular gland and pancreatic lesions using transcriptome-based deconvolution analysis. METHODS: Bulk RNA sequencing data were obtained from patients with IgG4-related submandibular sialadenitis (n = 40) and autoimmune pancreatitis (n = 8). Immune cell fractions were estimated using CIBERSORTx with the LM22 immune signature matrix. Relative immune cell compositions were compared descriptively, and exploratory Mann-Whitney U tests with false discovery rate (FDR) adjustment were performed. RESULTS: Both tissues shared broad immune cell repertoires, including B cells, T cells, macrophages, dendritic cells, mast cells, and natural killer cells, indicating a common immune framework across IgG4-RD lesions. However, organ-specific differences in relative immune cell abundance were observed. Pancreatic lesions showed a tendency toward increased macrophage populations, particularly M1-like macrophages, together with relatively reduced naïve B-cell fractions. In contrast, submandibular gland lesions demonstrated relatively enriched B-cell populations, including naïve and memory B cells, with a more balanced macrophage distribution. These patterns were consistently observed across samples and supported by deconvolution confidence metrics. CONCLUSIONS: IgG4-RD lesions share common immunological features while exhibiting differences in relative immune cell composition across tissues. Pancreatic lesions tended to show relatively increased macrophage fractions, whereas submandibular gland lesions demonstrated a more lymphocyte-rich immune profile. These findings suggest that local tissue context may shape immune composition and contribute to clinical heterogeneity in IgG4-RD.