High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins

Alexandre W. S. de Souza, Kornelis S. M. van der Geest, Elisabeth Brouwer, Frederico A. G. Pinheiro, Ana Cecília Diniz Oliveira, Emília Inoue Sato, Luis Eduardo C. Andrade, Marc Bijl, Johanna Westra, Cees G. M. Kallenberg

Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) which usually present as granulomatous inflammation in arterial walls. High mobility group box-1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. Twenty nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and in part of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10)ng/ml vs. 1.46 (0.89-3.34)ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16)ng/ml vs. 0.75 (0.39-2.05)ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46)ng/ml vs. 1.93 (0.88-3.34)ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.