Assessment of serum nitrite as biomarker of disease activity in ankylosing spondylitis

Abstract

Background The assessment of disease activity in patients with ankylosing spondylitis (AS) continues to be a challenging issue. The currently available markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) show poor correlation with clinical disease activity. There is a need for good biomarkers to assess disease activity. We explored serum nitrite, a stable end product of metabolism of NO, which is known to rise in inflammation, as a potential biomarker of disease activity in AS. Objectives To compare the levels of serum nitrite between patients with AS and healthy controls and to correlate levels of serum nitrite with disease activity in four assessment in ankylosing spondylitis (ASAS) domains. Methods Fifty patients satisfying modified New York criteria for AS were recruited for the study. Patients were assessed in the following ASAS domains: physical function (BASFI), pain (VAS, 0–100), patient global assessment (VAS, 0–100) and inflammation (mean of the two morning stiffness related BASDAI scores). Eighty-seven healthy controls were also included for comparison. Blood samples (12 hours fasting) were obtained and stored for serum nitrite level estimation, which was done by Ding's method. The median levels of serum nitrite were compared between the two groups. Correlation of serum nitrite levels was sought with individual domains of disease activity. Results The median serum nitrite levels in patients with AS were markedly elevated as compared to those in controls (39 μmol/L [IQR 27–50] vs. 4.75 μmol/L [2.53–12], P = 0.001 (Mann-Whitney U test). There was only one patient whose serum nitrite level overlapped with that of controls. Clinical assessment of disease activity (individual ASAS domains-physical function (BASFI), pain, patient global assessment and inflammation (mean of the two morning stiffness) did not show a good correlation with serum nitrite levels. Conclusions Serum nitrite level was increased eight folds in patients with AS when compared with controls. Thus its measurement holds promise in differentiating between inflammatory and mechanical low back pain. However, there was no variation across a range of levels of disease activity making it unsuitable as a biomarker to monitor disease activity in AS.