title: High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins.
abstract: BACKGROUND
  Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that 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.
  
  
  METHODS
  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 some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. alexandre_wagner@uol.com.br.|Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, R. Botucatu, 720, 04023 900, São Paulo, SP, Brazil. alexandre_wagner@uol.com.br.
authors.forename: Alexandre W S
authors.initials: AW
authors.lastname: de Souza
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. k.s.m.van.der.geest@umcg.nl.
authors.forename: Kornelis S M
authors.initials: KS
authors.lastname: van der Geest
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. e.brouwer@umcg.nl.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, R. Botucatu, 720, 04023 900, São Paulo, SP, Brazil. fredagp1@yahoo.com.br.
authors.forename: Frederico A G
authors.initials: FA
authors.lastname: Pinheiro
authors.affiliation: Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, R. Botucatu, 720, 04023 900, São Paulo, SP, Brazil. medceci@hotmail.com.
authors.forename: Ana Cecília Diniz
authors.initials: AC
authors.lastname: Oliveira
authors.affiliation: Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, R. Botucatu, 720, 04023 900, São Paulo, SP, Brazil. eisato@unifesp.br.
authors.forename: Emília Inoue
authors.initials: EI
authors.lastname: Sato
authors.affiliation: Rheumatology Division, Universidade Federal de São Paulo - Escola Paulista de Medicina, R. Botucatu, 720, 04023 900, São Paulo, SP, Brazil. luis.andrade@unifesp.br.
authors.forename: Luis Eduardo C
authors.initials: LE
authors.lastname: Andrade
authors.affiliation: Department of Internal Medicine and Rheumatology, Martini Hospital, Van Swietenplein 1, 9728, NT, Groningen, The Netherlands. m.bijl@mzh.nl.
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. johanna.westra@umcg.nl.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700, RB, Groningen, The Netherlands. c.g.m.kallenberg@umcg.nl.
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D013700:Giant Cell Arteritis / Q000097:blood*; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013625:Takayasu Arteritis / Q000097:blood*
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors