Serum MMP-2 and MMP-9 in patients with Behçet's disease: do their higher levels correlate to vasculo-Behçet's disease associated with aneurysm formation?

OBJECTIVES Basic and clinical studies have revealed a strong correlation between matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and the formation of abdominal aortic aneurysms. In addition, previous studies have clearly shown that MMP-2 and MMP-9 play an important role in the pathogenesis of vasculitis characterized by aneurysm formation such as Kawasaki disease, temporal arteritis and Takayasu arteritis. Depending on those findings, we hypothesized that circulating MMP-2 and MMP-9 could be useful markers to demonstrate vascular aneurysmatic involvement in patients with Behçet's disease (BD). METHODS Fifty-eight patients with BD, and 20 healthy controls were enrolled in the study. We assessed the disease activity of patients according to the Leeds activity score system. We compared the Leeds activity scores of patients with their serum levels of MMP2 and MMP-9. Patients with BD were categorized as active (total activity score > or = 5) or inactive (total activity score < 5). Patients were further categorized with respect to their extent of involvement as muco-cutaneous or systemic. Patients with systemic involvement were subdivided into ocular or vascular involvement. Patients with vascular involvement were subgrouped as thrombotic or aneurysmatic involvement. The levels of MMP-2 and MMP-9 were measured by ELISA. RESULTS Serum MMP-9 but not MMP-2 levels were significantly higher both in patients with active and inactive disease as compared to healthy controls (p = 0.008 and 0.013 respectively). We found positive correlation between Leeds activity score and serum MMP-2 levels in patients with vascular involvement (p = 0.035 and r = 0.485), and serum MMP-9 levels in active BD patients (p = 0.003 and r = 0.599). The serum levels of MMP-2 and MMP-9 in patients with systemic involvement were higher than those of healthy controls but not patients with mucocutaneous involvement (p = 0.046 and 0.002 respectively). The serum levels of MMP-2 in patients with vascular involvement were found to be higher than those of healthy controls and patients with mucocutaneous involvement (p = 0.001 and 0.003, respectively) but not different in those with ocular involvement. The serum levels of MMP-9 in patients with vascular involvement were found to be higher than those of healthy controls and ocular disease (p = 0.001 and 0.033 respectively) but not different in those with mucocutaneous involvement. The serum levels of MMP-2 in patients with aneurysmatic involvement were found to be higher than those of healthy controls, mucocutaneous and ocular involvement (p = 0.004, 0.008 and 0.004 respectively). The serum levels of MMP-2 in patients with thrombotic involvement were found to be higher than those of healthy controls and mucocutaneous (p = 0.018 and 0.033 respectively) but not ocular involvement. The serum levels of MMP-9 in patients with aneurysmatic involvement were found to be higher than those of healthy controls, mucocutaneous and ocular involvement (p = 0.001, 0.048 and 0.007 respectively). The serum levels of MMP-9 in patients with thrombotic involvement were found to be higher than those of healthy controls but not mucocutaneous and ocular involvement (p = 0.046). CONCLUSIONS We concluded that serum MMP-2 and MMP-9 levels can be used as an activity indicator for vasculo-Behçet's or active Behçet's patients, respectively. But they can not be used as a marker reflecting the systemic involvement of patients with BD. The systemic expressions of MMP-2 and MMP-9 were strongly associated with vasculo-Behçet's disease, particularly aneurysmatic involvement, suggesting their pathogenetic roles in vasculo-Behçet's disease complicated with aneurysm formation.