Abstract

Background: Incidence of late-onset rheumatoid arthritis (LORA) has been increasing recently. Patients with LORA have unique clinical characteristics compared to those with young-onset RA (YORA), but the underlying immunological condition is not understood. It is essential to elucidate the pathogenesis to develop an optimal treatment strategy for LORA. Objectives: To elucidate the differences in clinical characteristics, cytokine profiles and immunological conditions between patients with LORA and YORA. Methods: Consecutive patients with newly diagnosed, untreated RA between 2015 and 2022 and healthy controls were recruited. We measured serum 64 cytokines and chemokines and 56 immune cell subsets in their peripheral blood. We divided patients into two groups according to the onset age of 65 years old and compared the clinical and immunological characteristics between patients with LORA and YORA. Results: We enrolled 46 patients with LORA (median age, 74 years), 60 patients with YORA (median age, 49 years), and 14 healthy controls. Patients with LORA had significantly lower proportion of positivity for rheumatoid factor (57 vs 80%, p=0.02) and anti-cyclic citrullinated peptide antibody (52 vs 78%, p=0.007), higher proportion of acute onset (41 vs 3%, p<0.001), and higher levels of median C-reactive protein (2.5 vs 0.5 mg/dL, p<0.001) compared to those with YORA. We identified 16 cytokines or chemokines that significantly overexpressed in patients with LORA (p<0.05, Figure 1), and among them, interleukin (IL)-1 receptor antagonist, IL-6, IL-8, IL-15, vascular endothelial growth factor-A, tumor necrosis factor receptor (TNFR)-1, and TNFR-2 were significantly positively correlated with disease activity score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) in patients with LORA (p=0.01, p<0.001, p=0.005, p=0.02, p<0.001, respectively). Immunophenotyping revealed the number of naïve CD4 cells, naïve CD8 cells, IgD+ memory B cells, and transitional B cells were significantly lower in patients with LORA than those with YORA (p=0.005, p<0.001, p=0.006, and p=0.003, respectively). Number of B cell lineages including CD19+ B cells, naïve B cells, memory B cells, and transitional B cells were significantly inversely correlated with DAS28-ESR (p=0.03, p=0.01, p=0.03, and p=0.02, respectively) (Figure 1). Conclusion: LORA has distinct unique cytokine and immune cell profiles from YORA, which had close association with disease activity. Overexpression of inflammatory cytokines and immunosenescence, especially decrease in B cell lineages, may be associated with its unique clinical characteristics. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Satoshi Takanashi: None declared, Noriyasu Seki Employee of Mitsubishi Tanabe Pharma Corporation, Hideto Tsujimoto Employee of Mitsubishi Tanabe Pharma Corporation, Kenji Chiba Employee of Mitsubishi Tanabe Pharma Corporation, Yuko Kaneko: None declared.