In order to identify pathways related to the early development of rheumatoid arthritis (RA), we analyzed plasma samples from pre-symptomatic individuals, early RA patients, and 74 matched controls. The levels of proteins related to autoimmunity were measured using 153 antibodies. The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA). There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. Between pre-symptomatic individuals and RA patients, three hallmarks were identified: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. This confirmed the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provided a tool for a deeper understanding of molecules involved in the disease progression.
Mikael Brink, Anders Lundquist, Andrey Alexeyenko, Kristina Lejon and Solbritt Rantapää-Dahlqvist Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis Arthritis Research & Therapy (2019) 21:288 https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-019-2066-9