Clinical Study On Serological Markers And Imaging Performance Of Evaluating The Activity Of Takayasu 's Disease

Part I Evaluating the disease activity of MMP-3, MMP-9, IL-6and PTX-3in patients with Takayasu’s arteritisBackground Takayasu’s artertis (TA) is a chronic idiopathic vasculitis which primarily affects the aorta and its major branches, and women of reproductive age are most often affected, especially in China and Japan, In most patients, the disease onset and progress are insidious, and some systemic manifestations such as fever and weight loss often go unrecognized. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have generally been used as activity markers of TA disease, but they lack the sensitivity and specificity; therefore, alternative sensitive and conventional biomarkers of TA disease activity need to be identified, in order to aid early treatment.Objective To investigate whether matrix metalloproteinases(MMPs)(including MMP-3and MMP-9), interlukin-6(IL-6) as well as pentraxin-3(PTX-3) are potential biomarkers for the assessment of disease activity in patients with TA.Methods Forty-five patients diagnosed as TA during2010-01to2012-01at the department of Rheumathology, Zhongshan Hospital as well as10patients diagnosed as rheumathoid arthritis (RA) and twenty-five healthy donors were enrolled in this study. Circulating levels of MMP-3, MMP-9, IL-6and PTX-3were determined in both TA patients and healthy donors using enzyme linked immunosorbent assays (ELISAs). The relationships between these biomarkers and disease activity score and the sensitivity and specificity of these markers were simultaneously analyzed. In addition, clinical data, general laboratory such as ESR and CRP levels were collected simultaneously.Results Circulating levels of MMP-3, MMP-9, IL-6and PTX-3were significantly high in patients with TA than healthy donors; Additionally, MMP-9serum levels and PTX-3plasma levels were higher in patients of active phase than those of inactive phase, while MMP-3levels were lower in patients of active phase, and there was no significant difference of IL-6levels between active and inactive patients. MMP-9and PTX-3levels positively related to the disease activity score (Rho=0.80, p<0.01; Rho=0.78, p<0.01respectively), and both of them had high sensitivity and specificity in identifying the disease activity (the area of roc curve of MMP-9:0.97,95%CI0.93-1.0; the area of roc curve of PTX-3:0.95,95%CI0.89-1.00). Further more, in the combination of MMP-9and PTX-3, the sensitivity or specificity could be greatly improved. MMP-3levels negtively related to the disease activity score (Rho=-032, p=0.04).Conclusions MMP-9and PTX-3may be potential biomarkers with a high sensitivity and specificity for the assessment of disease activity in TA. Furthermore, MMP-3might play a protective roll in the disease process of TA. Part II The effect of the whole body magnetic resonance angiography in the assessment of disease activity and follow-up evaluation in patients with Takayasu’s arteritisBackground Various imaging technology has been used in the diagnosis of TA for years. However, commonly used methods such as arteriography, computerized tomography arteriography (CTA) and newly developed methods such as positron emission tomography/CT (PET/CT) and dual-energy CT had limitations in observing the lumen stenosis and/or wall thickness and enhancement. Recently, more and more attention has been put on the use of magnetic resonance imaging (MRI)/contrast-enhance MRI (CE-MRI) due to its specific characters. Previous studies have indicated the value of MRI in evaluating the inflammation of the artery and the disease activity of TA, though most studies were descriptive. Large-sample and quantitative study on the value of MRI in identifying the disease status and its use in the follow-up in patients with TA was insufficient.Objective To investigate the value of MRI in quantitatively identifying the disease activity and also to investigate the value of MRI in the follow-up in patients with TA.Methods Fifty-two patients diagnosed as TA during2010-01to2012-12at the department of Rheumatology, Zhongshan Hospital were enrolled in this study and MRI was done for each patient at the baseline. In fifteen patients, a second MRI was done after six months.Results Among the fifty-two patients, the most commonly involved arteries were carotid arteries, subclavian arteries, thoracic aorta, abdominal aorta and renal arteries. In comparison with inactive patients, the aortic arch involvement was more commonly seen (p=0.04). Furthermore, the lumen stenosis score, wall thickness and enhancement score on MRI were all positively related the disease activity score (p<0.05); the score of the lumen stenosis was also positively related to the circulating levels of MMP-9, IL-6, PTX-3, ESR, CRP and fibrinogen, and the score of the wall thickness had a positive relation with levels of MMP-9, PTX-3, ESR, CRP and fibrinogen; in addition, no relation was observed between MMPs, IL-6, PTX-3, ESR, CRP and the score of wall enhancement. During the follow-up, the results of MRI of the TA patients were not improved significantly.Conclusions MRI could be used to identifying the disease status quantitatively, and had favourable applying value for TA. Additionally, MRI comparison during the follow-up may indicate that the remission of the imaging would be hysteretic and the imaging results should be taken in to consideration when modulating the treatment.