Autoantibodies to high mobility group box 1 in patients with Incomplete and Systemic Lupus Erythematosus

Introduction. High Mobility Group Box-1 (HMGB1) is involved in the pathogenesis of Systemic Lupus Erythematosus (SLE). However, the role of autoantibodies to HMGB1 is unclear. Therefore levels of anti-HMGB1 and their reactivity to HMGB1 BoxA and BoxB were examined in association with disease activity and clinical parameters. Methods. Eighty-six SLE patients, 34 patients with incomplete lupus (ILE) and 44 age- and sex-matched healthy controls (HC) were included. Anti-HMGB1 levels were measured during quiescent disease (SLEDAI ≤4, n=47), and active disease (SLEDAI ≥5 n=39). Serum IgG, IgM anti-HMGB1 levels and reactivity against Box A and B were measured using ELISA. Results. Quiescent and active SLE patients had significantly increased anti- HMGB1 IgG levels compared to HC. There was no difference in anti-HMGB1 levels between active and quiescent patients. ILE patients did not have increased anti-HMGB1 levels. Anti-HMGB1 IgM in HC, ILE, quiescent and active SLE patients were comparable. There were no associations between anti-HMGB1 and disease activity, anti-ds DNA. However, patients with arthritis had higher anti- HMGB1 levels, while patients with neurological involvement had lower levels. Anti-HMGB1 levels were similar in active disease and subsequent remission. Patients with antibodies directed against both Box A and B had higher SLEDAI, increased anti-ds DNA, lower complement C3 levels, and higher total anti-HMGB1. Conclusion. Although anti-HMGB1 IgG levels are increased in SLE patients, no clear relation with disease activity or specific clinical symptoms was found. Therefore, anti-HMGB1 levels do not seem to be a useful biomarker of active disease or organ involvement.