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2015 ; 17
(ä): 338
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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
#MMPMID26596890
Wirestam L
; Schierbeck H
; Skogh T
; Gunnarsson I
; Ottosson L
; Erlandsson-Harris H
; Wetterö J
; Sjöwall C
Arthritis Res Ther
2015[Nov]; 17
(ä): 338
PMID26596890
show ga
INTRODUCTION: The 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. METHODS: 188 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. RESULTS: At 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. CONCLUSIONS: We 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.