Circulating PCSK9 relates to aggravated disease activity, Th17/Treg imbalance, and predicts treatment outcome of conventional synthetic DMARDs in rheumatoid arthritis patients.

backgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) regulates inflammatory response and CD4

methodsThis multi-center, prospective, cohort study determined serum PCSK9 in 89 RA patients who received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 50 healthy controls (HCs) after recruitment by enzyme-linked immunosorbent assay. For RA patients, serum PCSK9 was also determined at 6th week, 12th week, and 24th week; meanwhile, Th1, Th2, Th17, and Treg cells at baseline were determined through flow cytometry.

resultsPCSK9 was increased in RA patients compared to HCs (median: 209.2 versus 122.0 ng/mL, P < 0.001). In RA patients, PCSK9 positively correlated with Th17 cells (P = 0.023) and Th17/Treg ratio (P = 0.018), but did not link with Th1 cells, Th2 cells, Th1/Th2 ratio, or Treg cells. Meanwhile, PCSK9 was not associated with any demographics and medication histories, while it positively correlated with C-reactive protein (P = 0.010), disease activity score in 28 joints (P = 0.009), physician's global assessment (P = 0.015), and clinical disease activity index (P = 0.040). Importantly, PCSK9 gradually reduced from baseline to 24th week; its decrement related to higher possibility of treatment response (P = 0.002), low disease activity (P = 0.001), and remission of csDMARDs (P = 0.012).

conclusionCirculating PCSK9 shows the potency as a biomarker for disease management and treatment outcome prediction of csDMARDs in RA.