Soluble PD-1 as a key biomarker of disease activity in rheumatoid arthritis: a cross-sectional study at Tikur Anbessa Specialized Hospital

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial joints and destruction of bones. Various elements are involved in inflammation and disease progression. Various molecules are involved in inflammation and disease progression. Plasma neopterin and soluble programmed death-1 (sPD-1), which reflect immune activation and regulation, respectively, are central to RA pathogenesis. However, studies directly investigating the role of plasma neopterin and sPD-1 as biomarkers of RA are very limited. This study aimed to determine plasma neopterin and soluble programmed death-1 levels as biomarkers of RA disease activity and to assess their correlation with clinical parameters. A hospital-based, cross-sectional study was performed on 50 RA patients and 30 healthy controls at Tikur Anbessa Specialized Hospital. Plasma levels of sPD-1 and neopterin were measured via ELISA, and their correlations with clinical parameters, including DAS28-ESR, RF serostatus, ESR, and joint counts, were determined using Spearman's rank correlation. In RA patients, median plasma sPD-1 was 1022.61 pg/mL (IQR 870.23-1299.54) and mean neopterin was 9.258 ± 0.505 nmol/L, both higher than in healthy controls. sPD-1 correlated positively with DAS28 (r = 0.716, p < 0.001), ESR (r = 0.566, p < 0.001), and joint counts (r = 0.553, p < 0.001), indicating it may reflect disease activity. Active RA patients (DAS28 ≥ 2.6) had significantly higher sPD-1 levels than those in remission (p = 0.004). Neopterin was not associated with disease activity but was higher in RF-positive patients (mean 9.916 vs. 6.907 nmol/L; p = 0.0015), suggesting that both biomarkers are associated with more severe disease. Plasma sPD-1 is associated with RA disease activity and may be a valuable biomarker for evaluating patient condition and treatment outcomes. Although neopterin levels are elevated in individuals with RA, they often do not correlate strongly with disease activity. These findings highlight that neopterin is more involved in immune activation than in disease severity. In contrast, sPD-1 shows promise as a diagnostic marker and potential treatment target for RA. Future longitudinal studies should focus on sPD-1 and neopterin to better understand their roles in disease progression and response to therapy. Validating these biomarkers across larger and more diverse populations is essential to account for potential population differences and to develop personalized treatment strategies.