Serum Matrix Metalloproteinase-8 and -9 Levels in Disseminated Lyme Borreliosis with Special Reference to Arthritis

Abstract

Recent evidence suggests that matrix metalloproteinases (MMPs) are involved in pathogenesis of Lyme borreliosis (LB). We studied serum levels of MMP-8 and MMP-9 in disseminated LB patients with special reference to arthritis. Serum MMP-8 and-9 levels were analyzed by enzyme-linked immunoabsorbent assay from 110 patients from our previous multicenter, prospective study. Serum samples were taken before betalactam antibiotic treatment at study entry and after antibiotic treatment, at 1 year follow-up.Among disseminated LB patients (n = 110) mean (± SEM) serum MMP-8 and -9 levels (ng/ml) at study entry were statistically significantly higher than at 1 year follow-up (28.0 ± 1.9 versus 23.1 ± 1.6, P = 0.0313 and 398.0 ± 22.7 vs. 334.3 ± 23.6, P = 0.0219, respectively). Among Lyme arthritis (LA) patients (n = 34) at study entry serum MMP-8, but not MMP-9, levels decreased significantly when compared to serum levels of those at 1 year follow-up (35.7 ± 4.4 vs. 22.4 ± 2.3, P = 0.0093 and 398.6 ± 44.1 vs. 297.8 ± 40.3, P = 0.0505, respectively). The mean (± SEM) serum levels (ng/ml) of MMP-8 were significantly higher after betalactam antibiotic treatment at 1 year follow-up among antibiotic resistant LA patients with poor response than among those LA patients who were totally recovered (32.8 ± 6.4 vs. 20.1 ± 2.3, P = 0.0376). In contrast, the mean (± SEM) serum levels (ng/ml) of MMP-9 of antibiotic resistant LA patients showed no statistical significant difference when compared to those LA patients who were totally recovered at 1 year follow-up (297.8 ± 40.3 vs. 396.8 ± 93.9, P = 0.80).In conclusion, our results suggest that serum MMP-8 levels are excessively upregulated in disseminated LB contributing to inflammatory response, and related to persistent joint symptoms. This novel finding may offer in the future new laboratory possibilities to diagnose patients with persistent symptoms after betalactam antibiotic treatment. In addition the present findings suggest that to improve the outcome of disseminated borreliosis, the therapy of disseminated LB should include MMP-8 inhibitor such as doxycycline, possibly in combination therapy such as a combination of ceftriaxone and doxycycline. BIO © [2012], Copyright CCAAS Anneli Lauhio, et. al., BIO 2012, 2, 68-74 69 http://ccaasmag.org/BIO