ER-Golgi dysfunction and vesicular transport alterations in rheumatoid arthritis immune cells

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by immune cell dysfunction. The endomembrane system, consisting of the endoplasmic reticulum (ER) and Golgi apparatus (GA), plays a central role in protein synthesis and trafficking.

However, the regulatory architecture of the ER-Golgi axis in RA immune cells remains incompletely understood.MethodsWe performed an integrative multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from 96 RA patients and 90 healthy controls (HCs). Proteomic data were obtained from a previously published study from our research group, and transcriptomic data were retrieved from the GEO database (GSE17755).

Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Kinase activity and related signaling molecules were identified based on the functional annotations of differentially expressed proteins and phosphoproteins.

Upstream transcription factor (TF) regulatory networks were built through integration with hTFtarget. Drug candidates were screened using the DSigDB database.ResultsRA immune cells exhibited coordinated dysregulation of the ER-Golgi axis.

Proteomics revealed downregulation of vesicular transport components (RAB1A, SEC16A) and upregulation of ER stress-related proteins (DNAJC3, SERPINH1).