Anti-high mobility group box 1 (anti-HMGB1) antibodies are not related to the occurrence of cutaneous lesions in systemic lupus erythematosus

Tan, Guang; Zhu, Neng‐Xiu; Shi, Zhengang; Meng, Zhen; Yu, Man; Li, K; Yin, Jun; Wei, Kaihua; Mi, Xiangbin; Wang, L

doi:10.3109/03009742.2014.928946

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…Previous studies have also demonstrated increased anti-HMGB1 levels in SLE patients [5,[9][10][11], and in a small study more specific antibodies directed to box A [10]. In this study it was shown that through epitope mapping multiple HMGB1 epitopes were recognized in SLE sera, with the major epitope mapping box A.…”

Section: Discussionsupporting

confidence: 54%

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Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

Schaper

Leeuw

Horst

et al. 2017

Clinical and Experimental Immunology

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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.

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Section: Discussionsupporting

confidence: 54%

“…Autoantibodies against HMGB1 have been observed in patients with SLE [5,[9][10][11]. The clinical and/or pathological relevance of anti-HMGB1 antibodies is unclear, but their presence can interfere with the detection of HMGB1 in enzyme-linked immunosorbent assay (ELISA) systems [5,12].…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

Schaper

Leeuw

Horst

et al. 2017

Clinical and Experimental Immunology

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“…Anti-HMGB1 antibodies have previously been reported in SLE patients [ 26 , 31 , 32 ] and there are also a few reports on elevated HMGB1 levels in SLE [ 24 – 26 , 40 ]. However, the clinical value and possible role of anti-HMGB1 antibodies in the pathogenesis of SLE remains elusive and further studies on this matter are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Serum levels of HMGB1 are elevated in SLE patients and have been found to correlate positively with disease activity [ 24 – 27 ], and inversely with levels of complement proteins C3 and C4 [ 26 , 28 ]. HMGB1 may also serve as an autoantigen, leading to the production of anti-HMGB1 antibodies [ 26 , 29 – 32 ]. Anti-HMGB1/HMGB2 antibodies were first described as a type of “perinuclear” anti-neutrophil cytoplasm antibody (ANCA) in ulcerative colitis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Anti-HMGB1/HMGB2 antibodies were first described as a type of “perinuclear” anti-neutrophil cytoplasm antibody (ANCA) in ulcerative colitis [ 29 ]. Circulating anti-HMGB1 antibodies have also been reported in SLE [ 26 , 30 – 32 ] where the antibody levels appear to correlate with the SLE disease activity index (SLEDAI) and coincide with renal involvement [ 26 ]. However, the possible biological/clinical importance of anti-HMGB1 antibodies remains to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus

et al. 2015

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IntroductionThe non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodies can ameliorate murine polyarthritis and lupus-like disease. Interestingly, autoantibodies against HMGB1 have also been described in patients with systemic lupus erythematosus (SLE), but their clinical implications remain elusive. The main aims of this study were to detect serum anti-HMGB1 antibodies in patients with SLE and relate them to other types of antinuclear antibodies (ANA), and to disease activity.Methods188 Swedish SLE patients meeting the 1982 American College of Rheumatology classification criteria and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria participated in the study. Anti-HMGB1 antibody levels were analysed in patient and control (n = 112) sera by an in-house ELISA using recombinant histidine-tagged HMGB1. SLE sera were also analysed for ANA by immunofluorescence (IF) microscopy (IF-ANA) using fixed HEp-2 cells, and by a line-blot assay for antigen fine-specificities. To quantify antibodies to double-stranded DNA, a fluoroenzyme-immunoassay was employed.ResultsAt inclusion, 23 % of the SLE patients were anti-HMGB1 antibody positive compared to 5 % of the controls. Anti-HMGB1 antibodies occurred in 49 % of the IF-ANA positive SLE patients, and in 34 % of IF-ANA negative cases (p = 0.004). Levels of anti-HMGB1 antibodies correlated with anti-dsDNA antibody levels (r = 0.49; p < 0.001). Significant, but less pronounced correlations were found regarding anti-HMGB1 and SLE disease activity index (SLEDAI-2K: r = 0.15; p = 0.04), classical complement function (r = -0.24; p = 0.002) and complement protein C4 (r = -0.23; p = 0.002). Average anti-HMGB1 antibody levels were significantly higher among patients with homogenous ± other IF-ANA staining patterns (median 180 AU) compared to IF-ANA negative cases (median 83 AU) (p = 0.004). Rabbit anti-HMGB1 antibodies gave rise to cytoplasmic, but not nuclear, staining of HEp-2 cells.ConclusionsWe confirm that anti-HMGB1 antibodies are common in SLE and correlate with disease activity variables. Although anti-HMGB1 antibodies measured by ELISA often coincide with nuclear IF-ANA staining, our results indicate that anti-HMGB1 antibodies do not give rise to nuclear staining of the predominantly used commercial HEp-2 cell slides.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0856-2) contains supplementary material, which is available to authorized users.

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Pathogenesis of cutaneous lupus erythema associated with and without systemic lupus erythema

Zhang

Han

et al. 2017

Autoimmunity Reviews

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Anti-high mobility group box 1 (anti-HMGB1) antibodies are not related to the occurrence of cutaneous lesions in systemic lupus erythematosus

Abstract: Based on the findings of the current study, it is unlikely that anti-HMGB1 antibodies play a role in the development of SLE cutaneous lesions.

Cited by 9 publications

References 30 publications

Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

Autoantibodies to box A of high mobility group box 1 in systemic lupus erythematosus

Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus

Pathogenesis of cutaneous lupus erythema associated with and without systemic lupus erythema

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