Plasma haem oxygenase-1 may represent a first-in-class biomarker of oxidative stress in rheumatoid arthritis.

Objectives: This study explores the early identification of rheumatoid arthritis (RA) patients at elevated risk of progression. Haem-oxygenase-1 (HO-1) is a marker of oxidative stress in inflammation. Here, we investigate HO-1 as a biomarker of oxidative stress and its association with clinical disease activity and radiographic progression in RA.

Method: Baseline HO-1 was measured sequentially in plasma samples from patients with early rheumatoid arthritis (eRA) (n = 80). Disease Activity Score based on 28-joint count-C-reactive protein, Clinical Disease Activity Index, and total Sharp score were used to evaluate the disease course serially over 2 years. Paired plasma and synovial fluid samples were examined for HO-1 in active established rheumatoid arthritis (esRA) (n = 20). Plasma from healthy control subjects was also included (n = 35).

Results: Plasma HO-1 levels were increased in eRA {1373 pg/mL [interquartile range (IQR) 1110-2050]} and esRA [2034 pg/mL (IQR 1630-2923)] compared with controls [1064 pg/mL (IQR 869.5-1378)]. HO-1 plasma levels decreased with treatment. Baseline HO-1 correlated with disease activity and radiographic progression. A strong, linear correlation was found between synovial and plasma HO-1 levels (r = 0.75, p < 0.001).

Conclusion: In eRA, plasma levels of HO-1 were increased and correlated with disease and radiographic progression. A baseline measurement of plasma HO-1 levels demonstrated superior performance to currently used clinical and serological disease markers in the prediction of radiographic progression. Plasma HO-1 may function as a first-in-class biomarker of synovial oxidative stress in RA.