Abstract
Objective. GCA, a systemic vasculitis, is characterized by an IL-6-dependent acute-phase response. This response is typically suppressed by treatment rendering CRP/ESR unreliable for monitoring vascular inflammation. Also, there are no accurate biomarkers predicting a non-favourable disease course. Here we investigated macrophage products and markers of angiogenesis as biomarkers for prognosis and monitoring of vascular inflammation.
Methods. Forty-one newly diagnosed, glucocorticoid-naive GCA patients were prospectively followed for relapses and glucocorticoid requirement for a median of 30 months (range 0-71). Serum markers at baseline and during follow-up were compared with 33 age-matched healthy controls and 13 infection controls. Concentrations of IL-6, serum amyloid A, soluble CD163, calprotectin, YKL-40, VEGF, angiopoietin-1 and -2 and sTie2 were determined by ELISA/Luminex assay.
Results. Serum concentrations of all markers, but not angiopoietin-1, were elevated in GCA patients at baseline when compared with healthy controls. High VEGF (P = 0.0025) and angiopoietin-1 (P = 0.0174) and low YKL-40 (P = 0.0369) levels at baseline were predictive of a short time to glucocorticoid-free remission. Elevated angiopoietin-2 levels were associated with an imminent relapse during treatment (P <0.05). IL-6 correlated strongly with acute-phase markers and soluble CD163 but not with markers of angiogenesis, YKL-40 or calprotectin. Glucocorticoid treatment down-modulated all markers except for calprotectin and YKL-40. Tissue expression of markers in temporal arteries was confirmed.
Conclusion. Markers of angiogenesis at baseline and during treatment predict GCA disease course, suggesting utility in patient stratification for glucocorticoid-sparing therapy. Calprotectin and YKL-40 are candidate markers for monitoring vessel wall inflammation.
Original language | English |
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Pages (from-to) | 1383-1392 |
Number of pages | 10 |
Journal | Rheumatology |
Volume | 58 |
Issue number | 8 |
Early online date | 25-Feb-2019 |
DOIs | |
Publication status | Published - Aug-2019 |
Keywords
- angiogenesis
- angiopoietin-2
- biomarkers
- calprotectin
- giant cell arteritis
- glucocorticoids
- IL-6
- macrophages
- VEGF
- YKL-40
- ERYTHROCYTE SEDIMENTATION-RATE
- TOCILIZUMAB
- ACTIVATION
- PROTEIN