High-mobility group box 1, early activity marker in lupus nephritis

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Abstract

Objectives
Systemic lupus erythematosus is an autoimmune disease characterized by the involvement of multiple organ systems. High-mobility group box 1 (HMGB1) is a nuclear nonhistone protein secreted by many cells during activation or cell death. We aim to study the potential pathogenetic role of HMGB1 in lupus and whether urinary, serum, and renal biopsy levels reflect renal inflammation and correlate with disease activity.
Patients and methods
In a case–control study, 61 systemic lupus patients and 18 healthy volunteers were divided into four groups. Group 1 included 21 patients with lupus nephritis (LN). Group 2 included 21 patients with lupus activity without nephritis. Group 3 included 19 patients without activity. Group 4 included 18 healthy volunteers who were age and sex matched. Participants were subjected to assessment of history, physical examination, activity scoring using SLE disease activity index (SLEDAI), and laboratory investigations including plasma and urinary levels of HMGB1 by enzyme-linked immunosorbent assay. Study of the HMGB1 immunohistochemical expression pattern in renal biopsy was carried out in group 1.
Results
Plasma and urinary HMGB1 levels and the renal tissue extranuclear expression (cytoplasmic and extracellular) pattern of HMGB1 were significantly increased in patients with active LN compared with the other groups (<0.001), and were significantly correlated with SLEDAI, suggesting active release of HMGB1. Plasma and urinary levels in patients without active LN were also significantly higher compared with the control group (<0.001).
Conclusion
HMGB1 plays an important role in the pathogenesis of LN and reflects disease activity. Thus, HMGB1 can be utilized as a biomarker for renal disease activity in patients with lupus and the therapeutic value of HMGB1-blocking agents must be investigated.

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