THU0042 Autoantibodies against High Mobility Group Box Protein-1 in Systemic Lupus Erythematosus: Association with Disease Activity and Other Antinuclear Antibodies
Authors: C. Sjöwall, L. Wirestam, J. Wetterö, L. Ottosson, E. Sundberg, T. Skogh, H. Schierbeck
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a systemic autoimmune condition characterized by reduced ability to degrade and eliminate apoptotic cells. This probably contributes to the excessive production of antinuclear autoantibodies (ANA), including anti-double-stranded (ds) DNA, which is a hallmark of SLE. The non-histone nuclear protein high mobility group box protein-1 (HMGB1) can act as a pro-inflammatory mediator in many inflammatory diseases when released extracellularly. In SLE, HMGB1 may leak out from inefficiently degraded apoptotic cells and be involved in the pathogenesis [1]. Serum levels of HMGB1 correlate with SLE disease activity [2], and HMGB1 has also been shown to contribute to anti-dsDNA antibody production [3]. Anti-HMGB1 antibodies have been reported in SLE [2, 4], although their pathogenetic role remains elusive. <h3>Objectives</h3> We aimed to detect and evaluate anti-HMGB1 antibodies in relation to other autoantibodies and to disease activity, phenotypes and organ damage in a well-characterized cohort of Swedish SLE patients. <h3>Methods</h3> Sera from 188 SLE patients meeting the 1982 ACR and/or the 2012 SLICC classification criteria (89% female; mean age 49 years/range 18-88; mean duration 11 years/range 0-45) and 112 healthy controls (91% female; mean age 47 years/range 19-84) were included. Anti-HMGB1 antibody levels were analyzed by an in-house ELISA using recombinant HIS-tagged HMGB1. The cut-off value (300 AU) was set 2 standard deviations above the mean value among healthy controls. SLE sera were also analyzed by immunofluorescence microscopy with regard to ANA (IF-ANA) using fixed HEp-2 cells (ImmunoConcepts, Sacramento, US). Fluoroenzyme-immunoassay was used to evaluate anti-dsDNA antibodies (EliA, ThermoFischer, Uppsala, Sweden), and line-blot technique (ANA profile-5, Euroimmun, Lübeck, Germany) was used for other ANA fine specificities. <h3>Results</h3> 23% (43/188) of the SLE patients were judged anti-HMGB1 antibody positive versus 4% (5/112) of the controls. The levels of anti-HMGB1 were significantly higher in patients compared to controls. Anti-HMGB1 antibodies were associated with anti-dsDNA antibody (EliA) levels (r=0.49; <i>p</i>&lt;0.001), whereas correlations were less pronounced regarding SLEDAI-2K (r=0.15; <i>p</i>=0.04) and albuminuria (r=-0.18; <i>p</i>=0.02), classical complement function (r=-0.24; <i>p</i>=0.002) and complement protein C4 (r=-0.23; <i>p</i>=0.002). The presence of anti-HMGB1 was not associated with organ damage or distinct disease manifestations. Sera containing anti-HMGB1 antibodies were more likely to contain IF-ANA yielding chromatin staining (homogenous) on HEp-2 cells, compared to anti-HMGB1 negative samples (<i>p</i>=0.009). <h3>Conclusions</h3> We confirm that anti-HMGB1 antibodies occur in SLE and that they predominantly associate with a homogenous IF-ANA staining pattern. We did not find association with renal disease. Anti-HMGB1 levels were correlated with both clinical and serological signs of disease activity. <h3>References</h3> Urbonaviciute V, et al. J Exp Med 2008;205:3007-18. Abdulahad DA, et al. Arthritis Res Ther 2011;13:R71. Wen Z, et al. J Immunol 2013;190:5411-22. Hayashi A, et al. Mod Rheumatol 2009;19:283-92. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2533