title: Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus.
abstract: 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.
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Schaper
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: K
authors.identifier: 0000-0003-0218-9364
authors.initials: K
authors.lastname: de Leeuw
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Horst
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Maas
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Bootsma
authors.affiliation: Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Heeringa
authors.affiliation: Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: Limburg
authors.affiliation: Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Westra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003176:Complement C3 / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000097:blood; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D003176:Complement C3; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D007074:Immunoglobulin G
keywords: HMGB1; SLE; anti-HMGB1; anti-box A; autoantibodies