title: Is serum HMGB1 a biomarker in ANCA-associated vasculitis?
abstract: BACKGROUND
  Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are systemic inflammatory disorders that include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), Churg-Strauss syndrome and renal limited vasculitis (RLV). Extracellular high-mobility group box 1 (HMGB1) acts as an alarmin and has been shown to be a biomarker of disease activity as well as an autoantigen in systemic lupus erythematosus (SLE) and, possibly, in AAV. This study aims to assess antibodies against HMGB1 and HMGB1 levels as biomarkers for AAV disease activity and predictors of relapsing disease.
  
  
  METHODS
  AAV patients with active disease and healthy controls (HC) were evaluated for anti-HMGB1 antibodies while serum HMGB1 levels were measured longitudinally in AAV patients at presentation, during remission, prior to and at relapses.
  
  
  RESULTS
  HMGB1 levels were similar between AAV patients at presentation (n = 52) and HC (n = 35) (2.64 ± 1.80 ng/ml vs. 2.39 ± 1.09 ng/ml; P = 0.422) and no difference regarding HMGB1 levels could be found among AAV disease subsets (GPA: 2.66 ± 1.83 ng/ml vs. MPA: 3.11 ± 1.91 ng/ml vs. RLV: 1.92 ± 1.48 ng/ml; P = 0.369). AAV patients with renal involvement had lower HMGB1 levels than patients without renal involvement at presentation (2.35 ± 1.48 ng/ml vs. 3.52 ± 2.41 ng/ml; P = 0.042). A negative correlation was observed between HMGB1 levels and 24-hour proteinuria (ρ = -0.361, P = 0.028). Forty-nine AAV patients were evaluated for HMGB1 levels during follow-up and no differences were observed between relapsing and nonrelapsing patients (P = 0.350). No significant increase in HMGB1 levels was observed prior to a relapse compared with the remission period and changes in HMGB1 levels were not associated with an increased risk for relapse in AAV. Positivity for anti-HMGB1 antibodies was low in patients with active AAV (three out of 24 patients).
  
  
  CONCLUSIONS
  Serum HMGB1 levels at presentation are not increased and are lower in patients with renal involvement. Relapses are not preceded or accompanied by significant rises in HMGB1 levels and changes in HMGB1 levels are not related to ensuing relapses. Anti-HMGB1 antibodies are present in only a few patients in AAV. In contrast to SLE, HMGB1 is not a useful biomarker in AAV.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Souza
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.forename: Johan
authors.initials: J
authors.lastname: Bijzet
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Limburg
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
authors.forename: Marc
authors.initials: M
authors.lastname: Bijl
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000150:complications / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000097:blood* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000097:blood / Q000150:complications / Q000276:immunology; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D024243:HMGB1 Protein