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. 2011 May 6;13(3):R71.
doi: 10.1186/ar3332.

High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus

Deena A Abdulahad  1 , Johanna Westra, Johannes Bijzet, Pieter C Limburg, Cees G M Kallenberg, Marc Bijl
Affiliations

High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus

Deena A Abdulahad et al. Arthritis Res Ther. .

Abstract

Introduction: High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein. HMGB1, which is secreted by inflammatory cells and passively released from apoptotic and necrotic cells, may act as a pro-inflammatory mediator. As apoptotic cells accumulate in systemic lupus erythematosus (SLE), HMGB1 levels might be increased in SLE. HMGB1 may also serve as an autoantigen, leading to the production of anti-HMGB1 antibodies. In this study we determined levels of HMGB1 and anti-HMGB1 in SLE patients in comparison to healthy controls (HC) and analysed their relation with disease activity.

Methods: The study population consisted of 70 SLE patients and 35 age- and sex-matched HC. Thirty-three SLE patients had quiescent disease, the other 37 patients were selected for having active disease. Nineteen of these had lupus nephritis. HMGB1 levels were measured with both Western blot and ELISA. Anti-HMGB1 levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures.

Results: HMGB1 levels in SLE patients could be measured reliably by Western blotting only, and were significantly increased compared to HC. During active disease HMGB1 levels increased, in particular in patients with renal involvement. Serum HMGB1 levels correlated with SLEDAI, proteinuria, and anti-dsDNA levels, and showed a negative correlation with complement C3. Anti-HMGB1 levels were significantly increased in SLE patients compared to HC, and positively correlated with HMGB1 levels.

Conclusions: Levels of HMGB1 in the sera of SLE patients, in particular in those with active renal disease, are increased. Serum HMGB1 levels are related to SLEDAI scores and proteinuria, as well as to levels of anti-HMGB1 antibodies. These findings suggest that besides HMGB1, HMGB1-anti-HMGB1 immune complexes play a role in the pathogenesis of SLE, in particular in patients with renal involvement.

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Figures

Figure 1
Figure 1
HMGB1 concentrations in sera from SLE patients and healthy controls (HC). A) Serum HMGB1 levels in SLE patients and HC using ELISA. Horizontal lines represent the median. B) Serum HMGB1 levels of SLE patients and HC measured by Western blot. C) HMGB1 levels measured by Western blot in active patients with renal manifestations and with those without renal manifestations.
Figure 2
Figure 2
Serum HMGB1 after IgG depletion. HMGB1 levels are decreased in serum depleted of IgG from an SLE patient. The first lane represents the standard control consisting of human keratinocyte HaCaT cells; the second lane represents the HMGB1 amount in the serum of a SLE patient before IgG depletion and in the third lane the HMGB1 amount after IgG depletion in the serum of same patient is shown.
Figure 3
Figure 3
Anti-HMGB1 levels in SLE patients and their relation to HMGB1. A) Anti-HMGB1 levels in SLE patients compared to HC. Horizontal lines represent the levels expressed as median. B) Positive correlation between levels of HMGB1 and anti-HMGB1 antibodies.
Figure 4
Figure 4
Correlation of SLEDAI scores with levels of HMGB1 and anti-HMGB1 antibodies in SLE patients. A) SLEDAI scores correlate positively with HMGB1 levels as well as with B) Anti-HMGB1 antibody levels.
Figure 5
Figure 5
Correlations of HMGB1 and anti-HMGB1 antibodies with anti-dsDNA antibodies, C3 and C4 in SLE patients
Figure 6
Figure 6
Correlation of HMGB1 levels with proteinuria in SLE patients
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References

    1. Shirai T, Hirose S. Molecular pathogenesis of SLE. Springer Semin Immunopathol. 2006;28:79–82. doi: 10.1007/s00281-006-0032-5. - DOI - PubMed
    1. Abdulahad DA, Westra J, Limburg PC, Kallenberg CG, Bijl M. HMGB1 in systemic lupus erythematosus: Its role in cutaneous lesions development. Autoimmun Rev. 2010;9:661–665. doi: 10.1016/j.autrev.2010.05.015. - DOI - PubMed
    1. Bergtold A, Gavhane A, D'Agati V, Madaio M, Clynes R. FcR-bearing myeloid cells are responsible for triggering murine lupus nephritis. J Immunol. 2006;177:7287–7295. - PubMed
    1. Schroeter AL, Conn DL, Jordon RE. Immunoglobulin and complement deposition in skin of rheumatoid arthritis and systemic lupus erythematosus patients. Ann Rheum Dis. 1976;35:321–326. doi: 10.1136/ard.35.4.321. - DOI - PMC - PubMed
    1. Tokumoto M, Fukuda K, Shinozaki M, Kashiwagi M, Katafuchi R, Yoshida T, Yanagida T, Kanai H, Hirakata H, Tamaki K, Okuda S, Fujishima M. Acute interstitial nephritis with immune complex deposition and MHC class II antigen presentation along the tubular basement membrane. Nephrol Dial Transplant. 1999;14:2210–2215. doi: 10.1093/ndt/14.9.2210. - DOI - PubMed

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