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High mobility group box-1 (hmgb1) in systemic vasculitides

The interplay with active disease, specific organ involvement and therapy
PhD ceremony:Mr A.W. (Alexandre) Silva de Souza
When:May 13, 2015
Supervisor:prof. C.G.M. Kallenberg
Co-supervisors:dr. M. Bijl, dr. J. (Hannie) Westra
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
High mobility group box-1 (hmgb1) in systemic vasculitides

In this thesis, we evaluated circulating high mobility group box 1 (HMGB1) levels in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), in large vessel vasculitis (LVV) and in Behçet’s disease (BD). AAV patients without renal involvement present serum HMGB1 levels higher than healthy controls (HC) but fluctuations of HMGB1 levels were not associated with disease relapses in AAV. Serum HMGB1 levels were not associated with atherosclerosis in carotid arteries whereas serum levels of the soluble receptor for advance glycation end-products (sRAGE) correlated negatively with overall maximum intima-media thickness (IMT). Statins were associated with lower serum HMGB1 levels and atorvastatin inhibited HMGB1 release by human umbilical vein endothelial cells (HUVEC) in vitro. Active nephritis in AAV was associated with higher urinary HMGB1 levels with a decrease after achieving remission. Urinary HMGB1 was associated with urinary CD4+ T cells and CD4+ effector memory T cells. In LVV, such as Takayasu arteritis (TA) and giant cell arteritis (GCA) we could not find differences in HMGB1 levels between patients and HC or between active disease and remission. Statins led to lower serum HMGB1 levels in TA patients. Patients with Behçet’s disease (BD) present higher serum HMGB1 levels than HC. However, there was no association with disease activity or specific organ involvement. In conclusion, serum HMGB1 levels are not a biomarker of disease activity in AAV and LVV, but urinary HMGB1 levels reflect active nephritis in AAV. In BD, serum HMGB1 levels are higher than in HC regardless of disease activity.