Active MMPs captured by alpha2Macroglobulin as a marker of disease activity in rheumatoid arthritis
article
Objective. The aim of the present study was to analyze α2Macroglobulin/MMP (α2M/MMP) complex formation and to investigate whether MMP activity in α2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA). Methods. High and low molecular weight (H/LMW) substrates and inhibitors and size exclusion were used to analyze α2M/MMP complex formation. LMW fluorogenic substrates were used to quantify the level of MMPs in α2M/MMP complexes in the serum of RA patients and healthy controls. Results. Active MMPs were fully inhibited by LMW inhibitor BB94 in the presence of α2M, whereas no inhibition was achieved by HMW inhibitor TIMP-1. Size exclusion analysis showed α2M/MMP complex formation in buffer and in normal plasma spiked with activated MMPs, whichFrom Subject Received Size Categories
Beheer-TNO-SharePoint NDIA Weekly Insider 8:00 18 KB indicated α2M/MMP complex formation in the systemic circulation. MMP activity in α2M/MMP complexes in the serum of RA patients was significantly higher than in the serum of healthy controls (P<0.001). MMP activity levels in the serum of RA patients were correlated with ESR (r = 0.72, P<0.001). Conclusion. In the systemic circulation of RA patients, active MMPs form complexes with α2M and can be detected using LMW fluorogenic substrates. MMP activity measurements in serum allow discrimination between RA patients and healthy controls and provide a new tool for the assessment of the disease process in RA.
Beheer-TNO-SharePoint NDIA Weekly Insider 8:00 18 KB indicated α2M/MMP complex formation in the systemic circulation. MMP activity in α2M/MMP complexes in the serum of RA patients was significantly higher than in the serum of healthy controls (P<0.001). MMP activity levels in the serum of RA patients were correlated with ESR (r = 0.72, P<0.001). Conclusion. In the systemic circulation of RA patients, active MMPs form complexes with α2M and can be detected using LMW fluorogenic substrates. MMP activity measurements in serum allow discrimination between RA patients and healthy controls and provide a new tool for the assessment of the disease process in RA.
Topics
Biomedical Researchα2MacroglobulinMatrix metalloproteasesRheumatoid arthritisAlpha 2 macroglobulinBatimastatCollagenase 3Matrix metalloproteinaseTissue inhibitor of metalloproteinase 1CirculationClinical articleComplex formationConcentration (parameters)Controlled studyCorrelation analysisDisease activityDisease courseDisease markerEnzyme linked immunosorbent assayErythrocyte sedimentation rateFast protein liquid chromatographyFluorescence analysisHumanMolecular weightPriority journalProtein analysisProtein blood levelQuantitative analysisRheumatoid arthritisAdultalpha-MacroglobulinsArthritis, RheumatoidBiological MarkersCase-Control StudiesDisease ProgressionEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMatrix MetalloproteinasesMiddle AgedProbabilityPrognosisReference ValuesSensitivity and SpecificitySeverity of Illness Index
TNO Identifier
237360
ISSN
0392856X
Source
Clinical and Experimental Rheumatology, 21(6), pp. 711-718.
Pages
711-718