Elevated serum concentrations of metalloproteinases (MMP-2, MMP-9) and their inhibitors (TIMP-1, TIMP-2) in patients with Graves’ orbitopathy

Background. Graves' orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is characterized by dramatic tissue reactivity. Both inflammation and tissue remodeling characterize the clinical course of GO. Some data has been found regarding the association of MMPs and TIMPs in GO.Material and Methods. Serum concentrations of MMP-9, MMP-2, TIMP-1, and TIMP-2 were determined by ELISA method.Objectives. Forty-eight patients (34 females, 14 males, with median age 51.5 years) with GD and hyperthyroidism were enrolled in the study. In 28 patients, active, moderate-to-severe grade orbitopathy was diagnosed. The aim of this study was to assess the serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 in patients with Graves' disease (GD), with and without GO, and their relationship with disease severity, as well as to evaluate how these concentrations change after successful treatment.Results. Median serum concentrations of MMP-2 and MMP-9 were significantly higher in all patients with GD as well as in the subgroup with GO than in the control group. Median serum concentrations of TIMP-1 and TIMP-2 were significantly higher in all patients with GD than in controls. The same significant differences were observed in the subgroups with and without GO in comparison with controls. The GO subgroup showed a significant positive correlation between the MMP-9 concentration and the serum level of TSHRAb antibodies, and a clinical activity score ≥4 according to EUGOGO.Conclusion. In our study we found that only MMP-9 differentiates the patients with and without GO, and may be used as a marker of the disease severity in patients with this manifestation of GD.