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THU0042 Autoantibodies against High Mobility Group Box Protein-1 in Systemic Lupus Erythematosus: Association with Disease Activity and Other Antinuclear Antibodies
  1. C. Sjöwall1,
  2. L. Wirestam1,
  3. J. Wetterö1,
  4. L. Ottosson2,
  5. E. Sundberg2,
  6. T. Skogh1,
  7. H. Schierbeck2
  1. 1AIR/Reumatologi, Department of Clinical and Experimental, Medicine, Linköping University, Linköping
  2. 2Paediatric Unit, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden

Abstract

Background 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.

Objectives 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.

Methods 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.

Results 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; p<0.001), whereas correlations were less pronounced regarding SLEDAI-2K (r=0.15; p=0.04) and albuminuria (r=-0.18; p=0.02), classical complement function (r=-0.24; p=0.002) and complement protein C4 (r=-0.23; p=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 (p=0.009).

Conclusions 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.

References

  1. Urbonaviciute V, et al. J Exp Med 2008;205:3007-18.

  2. Abdulahad DA, et al. Arthritis Res Ther 2011;13:R71.

  3. Wen Z, et al. J Immunol 2013;190:5411-22.

  4. Hayashi A, et al. Mod Rheumatol 2009;19:283-92.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2533

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