Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis

van Sleen, Y., Sandovici, M., Abdulahad, W. H., Bijzet, J., van der Geest, K. S. M., Boots, A. M. H. & Brouwer, E., Aug-2019, In : Rheumatology. 58, 8, p. 1383-1392 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)1383-1392
Number of pages10
Issue number8
Early online date25-Feb-2019
Publication statusPublished - Aug-2019


  • angiogenesis, angiopoietin-2, biomarkers, calprotectin, giant cell arteritis, glucocorticoids, IL-6, macrophages, VEGF, YKL-40, ERYTHROCYTE SEDIMENTATION-RATE, TOCILIZUMAB, ACTIVATION, PROTEIN

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