Diagnostic value of serum high-mobility group box-1 in pediatric systemic lupus erythematosus

Int J Rheum Dis. 2019 Aug;22(8):1402-1409. doi: 10.1111/1756-185X.13556. Epub 2019 Apr 2.

Abstract

Background: High-mobility group box-1 (HMGB1) acts as a damage-associated molecular pattern or as an alarmin and it stimulates inflammatory and immunological activities.

Aim: We sought to investigate serum HMGB1 protein expression in patients with pediatric systemic lupus erythematosus (pSLE) in relation to the disease characteristics and activity.

Patients and methods: This is a controlled cross-sectional study which comprised 50 children and adolescents with Systemic lupus erythematosus (SLE) and 50 age- and sex-matched healthy subjects who served as a control group. Study measurements included clinical assessment, laboratory workup for SLE (complete blood count, erythrocyte sedimentation rate, serum creatinine, creatinine clearance and 24-hour urinary protein, C3 and anti-double-stranded DNA, lupus anticoagulant and anticardiolipin antibodies) and measurement of serum HMGB1 by enzyme-linked immunosorbent assay in patients and controls.

Results: Serum HMGB1 expression was significantly higher in the pSLE patients than the control group (P < 0.001). Patients with lupus nephritis (LN) had significantly higher serum HMGB1 as compared to those with normal kidneys (P < 0.04). Serum HMGB1 in LN patients correlated positively to the SLE Disease Activity Index (P < 0.0001), and 24 hours urinary proteins and negatively to creatinine clearance (P < 0.001). At a cut-off point of ≥40 µg/L, serum HMGB1 showed good diagnostic value for pSLE with sensitivity and specificity of 98% and 95%, respectively.

Conclusion: Serum HMGB1 seems to be a reliable biomarker for diagnosis of pSLE and monitoring disease status, especially in LN. HMBG1 might prove to be a potential therapeutic target in LN.

Keywords: HMGB1; lupus nephritis; pediatric systemic lupus erythematosus.

MeSH terms

  • Adolescent
  • Age of Onset
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Cross-Sectional Studies
  • Female
  • HMGB1 Protein / blood*
  • Humans
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Nephritis / blood
  • Lupus Nephritis / diagnosis
  • Male
  • Predictive Value of Tests
  • Reproducibility of Results
  • Severity of Illness Index
  • Up-Regulation

Substances

  • Biomarkers
  • HMGB1 Protein
  • HMGB1 protein, human