Abstract 5797: New Biomarkers for Assessing the Activity of Takayasu Arteritis
Background - Takayasu arteritis (TA) is a chronic vasculitis, mainly involving the aorta and its main branches. Erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP)have generally been used for monitoring the disease activity. We frequently experience patients who show inflammatory symptoms without an elevation of CRP, even though they are treated with immunosuppressants. Therefore, we sought for useful and sensitive biomarkers to diagnose subtle activity of TA. We hypothesized that pentraxin3 (PTX3) and matrix metalloproteinases (MMPs) could be biomarkers of TA to detect patients who develop recurrence of the disease even in the absence of CRP elevation.
Methods and Results - Consecutive series of 45 patients with TA and 20 age-matched healthy controls were enrolled in this study. According to the clinical symptoms of the patients, 23 patients were in an active phase as evidenced by clinical recurrences within 2 years of blood sampling and 22 patients were in an inactive phase without any inflammation for more than 2 years. Circulating levels of PTX3, MMP-2, MMP-3 and MMP-9 were determined by ELISA. Patients in an active phase had significantly higher level of high sensitive CRP (hsCRP), PTX3, MMP-3 and MMP-9 than those in an inactive patients. Sensitivity (SE), specificity (SP) and area under the ROC curve (AUC) to detect active patients of each biomarker are as follows. hsCRP: SE 53.33%, SP 90.91%, AUC 0.798, PTX3: SE 76.19%, SP 76.19%, AUC 0.871. MMP-3: SE 60.87%, SP 86.36%, AUC 0.831, MMP-9: SE 61.90%, SP 66.67%, AUC 0.728. PTX3 was the best single marker with the highest diagnostic accuracy. Among 21 patients in an active phase, 9 patients showed negative hsCRP level (<4837ng/ml). However, PTX3 level was elevated (>5.27ng/ml) in 7 of the 9 patients. Patients with TA had significantly higher level of MMP-9 (active:360±75ng/ml, inactive:229±48ng/ml) than normal controls (23±5ng/ml) inspective of disease activity. Evaluation of MMP-9 may suggest prior existence of TA even in inactive patients.
Conclusions - PTX3, MMP-3 and MMP-9 could be new and sensitive biomarkers to estimate the activity of TA. We can predict recurrence of TA by elevation of PTX3 even patients whose CRP is negative.