A Preliminary Exploratory Study Based on LC–MS/MS and LFQ for Candidate Protein Biomarkers in Peripheral Blood from Rheumatoid Arthritis

Objective: Detangling the rheumatoid arthritis (RA) proteomic profile is of interest to improve diagnosis, RA subclassifications, and targeted treatment. We aimed at identifying serum proteins as candidate biomarkers for RA. Methods: This case-control study included participants with RA and healthy controls (HCs) paired by gender; clinical information and proteomic profiles were analyzed for the identification of candidate protein biomarkers. A statistical analysis included logistic regression and ROC curves for AUC measurement. Results: Following the screening of 176 patients, 25 RA and 25 HC patients were included in this study. The average age was 51 ± 12 years, and 90% were females. Notably, we identified five serum protein candidate biomarkers with differential expression when comparing RA to HC, consisting of testis-expressed protein 13B (p = 6.31 × 10−4), keratin type II cytoskeletal 79 (p = 1.317 × 10−4), 60 kDa heat shock protein (p = 7.594 × 10−4), pseudo uridylate synthase 7 homolog (p = 8.332 × 10−3), and SUN domain-containing protein 3 (p = 1.883 × 10−7). The first four proteins were predominantly observed in patients with RA, while the last was predominantly identified in the HCs. Conclusions: A distinctive serum candidate biomarker profile consistent in five proteins was identified for RA, suggesting a unique stress-related, inflammatory signature. Collectively, the profile exhibits potential, but our findings must be validated in larger cohort studies, preferably in the context of undifferentiated arthritis before a definitive model for diagnosis is established.