Plasma levels of matrix metalloproteinase-9 in chronic urticaria patients correlate with disease severity and C-reactive protein but not with circulating histamine-releasing factors

Background Matrix metalloproteinase-9 (MMP-9) is an endopeptidase produced by many inflammatory cells that has been found in increased amounts in plasma from patients with chronic urticaria (CU). Objective To evaluate plasma levels of MMP-9 and its tissue inhibitor of metalloproteinase-1 (TIMP-1) in CU patients in relation with disease severity, C-reactive protein (CRP) and circulating histamine-releasing factors. Methods Fifty-two consecutive CU patients were included in the study and disease activity was graded from 0 to 3. Plasma MMP-9, TIMP-1 and CRP levels were measured by enzyme immunoassays. Circulating histamine-releasing factors were assessed using in vivo (autologous serum skin test) and in vitro (basophil histamine release) tests. Seven CU patients were studied both during active disease and during remission. Thirty healthy subjects were used as normal controls. Results Plasma levels of MMP-9, TIMP-1 and CRP were significantly higher in CU patients than in healthy controls (P = 0.0001, 0.003 and 0.005, respectively) and a trend towards a higher MMP-9/TIMP-1 molar ratio was found (P = 0.051). A significant correlation was found between plasma MMP-9 levels and urticaria severity score (r = 0.48, P<0.0001). CRP levels correlated with MMP-9 levels (r = 0.37, P = 0.008) and CU severity score (r = 0.52, P = 0.0001), but not with TIMP-1 (r = 0.13) concentrations. MMP-9, TIMP-1 and CRP plasma levels and MMP-9/TIMP-1 molar ratio did not differ in patients either with or without an evidence of circulating histamine-releasing factors. Seven patients evaluated during remission showed a significant reduction of MMP-9 and CRP plasma levels. Conclusion Plasma levels of MMP-9 and its inhibitor TIMP-1 are increased in CU patients. MMP-9 levels are associated with disease severity and CRP levels, but not with skin reactivity to autologous serum and with circulating histamine-releasing factors. These findings suggest that in CU there is an ongoing inflammatory process independent of the presence of circulating histamine-releasing factors.