Integrative analysis reveals the role of THBS1 in IgG4-related disease

Abstract

Abstract Background: IgG4-related disease (IgG4-RD) is a heterogeneous immune-mediated fibroinflammatory disorder. By utilizing the Gene Expression Omnibus (GEO) database and single-cell sequencing data, we aimed to construct a comprehensive transcriptomic profile of IgG4-RD and identify hub genes involved in its pathogenesis. Results: IgG4-RD-related differentially expressed genes were found to be coenriched in immune- and platelet-related biological functions or signaling pathways. WGCNA analysis showed that five hub genes (GNG11, PDE5A, PLK2, PROS1, and thrombospondin 1 [THBS1]) were upregulated in LSG and PBMCs. Further analysis of the protein–protein interaction network revealed that THBS1 was the key gene. Plasma THBS1 levels were significantly elevated in patients with IgG4-RD compared with those in healthy controls (p< 0.0001). Immune infiltration analysis revealed a correlation between THBS1expression and various immune infiltrating cells. Single-cell sequencing analysis indicated that THBS1 was predominantly expressed in classical monocytes of PBMCs derived from patients with IgG4-RD. Conclusion: This study revealed the potential pathogenic mechanisms of THBS1 in IgG4-related disease and identified THBS1 as a potential diagnostic biomarker for the disease.