Matrix Metalloproteinases and Their Tissue Inhibitors: an Evaluation of Novel Biomarkers in ANCA-Associated Vasculitis

Zakiyanov, Oskar; Chocová, Z.; Hrušková, Z.; Hladinová, Z.; Kalousová, Marta; Malíčková, K.; Bednářová, V.; Vachek, J.; Wurmová, P.; Kříha, V.; Zima, T.; Tesař, V.

doi:10.14712/fb2019065050227

Folia Biologica > Archive > 2019, Vol. 65 > Issue 5-6 > Matrix Metalloproteinases and Their…

Fol. Biol. 2019, 65, 227-236

https://doi.org/10.14712/fb2019065050227

Matrix Metalloproteinases and Their Tissue Inhibitors: an Evaluation of Novel Biomarkers in ANCA-Associated Vasculitis

Oskar Zakiyanov¹, Z. Chocová¹, Z. Hrušková^1,2, Z. Hladinová¹, Marta Kalousová³, K. Malíčková³, V. Bednářová¹, J. Vachek¹, P. Wurmová¹, V. Kříha⁴, T. Zima³, V. Tesař¹

¹Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
²Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czech Republic
³Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
⁴Institute of Radiation Oncology, Bulovka Hospital, Prague, Czech Republic

Received July 2019
Accepted October 2019

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play an important role in both inflammation with subsequent fibrosis and in repair and healing in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We evaluated the circulating levels of MMPs, including pregnancy-associated plasma protein A (PAPP-A), and TIMPs in patients with AAV. PAPP-A, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, TIMP-2 and selected parameters were measured in 100 AAV patients (36 patients with active disease and 64 patients in remission) and 34 healthy subjects. The levels of MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, TIMP-2, and PAPP-A in AAV were all found to be different to those of the controls. The MMP-7 and PAPP-A concentrations were increased in active disease in comparison to the controls (MMP-7: 13 ±.7 vs. 2 ± 0.6 ng/ml, PAPP-A: 14 ± 18 vs. 6.8 ± 2.6 ng/ml, both P < 0.005). The MMP-2 and TIMP-2 levels were increased in remission when compared to the controls (MMP-2: 242 ± 50 ng/ml vs. 212 ± 26 ng /ml, TIMP-2: 82 ± 14 ng/ml vs. 68 ± 93 ng/ml) and to the active AAV (MMP-2: 242 ± 50 vs. 219 ± 54 ng/ml, TIMP-2: 82 ± 14 ng/ml vs. 73 ± 15 ng/ml, all P < 0.005). MMP-3, MMP-7, TIMP-1, and PAPP-A correlated with serum creatinine. The serum levels of MMPs, TIMPs and PAPP-A are all altered in AAV. MMP-2, MMP-7 and TIMP-2 appear to be promising markers in distinguishing active AAV from remission. MMP-3, MMP-7, TIMP-1, and PAPP-A are associated with kidney function in AAV. Further studies are needed to delineate the exact roles of circulating MMPs, TIMPs and PAPP-A in patients with AAV.

Keywords

anti-neutrophil cytoplasmic antibodies, vasculitis, matrix metalloproteinases, tissue inhibitors of metalloproteinases, pregnancy-associated plasma protein A.

Funding

This study was supported by the research project of Charles University Progres Q25/LF/1/2, MH CZ DRO VFN 64165, MH CZ DRO NNB 0064211, and SVV 260373.