Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus. (27th March 2017)

• Record Type: Journal Article
• Authors: Schaper, F; de Leeuw, K; Horst, G; Maas, F; Bootsma, H; Heeringa, P; Limburg, P C; Westra, J
• Is Part Of: Clinical and experimental immunology. Volume 188:Number 3(2017:Jun.)
• Page Start: 412
• Page End: 419
• Publication Date: 2017-03-27
• Subjects: anti-box A -- anti-HMGB1 -- autoantibodies -- HMGB1 -- SLE; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12951
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Autoantibodies to nuclear structures are a hallmark of systemic lupus erythematosus (SLE), including autoantibodies to nuclear protein high mobility group box 1 (HMGB1). HMGB1 consists of three separate domains: box A, box B and an acidic tail. Recombinant box A acts as a competitive antagonist for HMGB1 and might be an interesting treatment option in SLE. However, antibodies to box A might interfere. Therefore, levels of anti-box A were examined in SLE patients in association with disease activity and clinical parameters. Serum anti-box A was measured in 86 SLE patients and 44 age- and sex-matched healthy controls (HC). Serum samples of 28 patients with primary Sjögren's syndrome and 32 patients with rheumatoid arthritis were included as disease controls. Anti-HMGB1 and anti-box B levels were also measured by enzyme-linked immunosorbent assay during quiescent disease [SLE Disease Activity Index (SLEDAI) ≤ 4, n = 47] and active disease (SLEDAI ≥ 5, n = 39). Anti-box A levels in active SLE patients were higher compared to quiescent patients, and were increased significantly compared to HC and disease controls. Anti-box A levels correlated positively with SLEDAI and anti-dsDNA levels and negatively with complement C3 levels. Increased levels of anti-box A antibodies were present in the majority of patients with nephritic (73%) and non-nephritic exacerbations (71%). Antibodies to the box A domain of HMGB1 might be an interesting new biomarker, as these had a high specificity for SLE and were associated with disease activity. Longitudinal studies should be performed to evaluate whether these antibodies perform better in predicting an exacerbation, especially non-nephritic exacerbations. Graphical Abstract: