Vol.19 No.3

Original Article

Lupus antibodies to the HMGB1 chromosomal protein: epitope mapping and association with disease activity

Authors

Ayako Hayashi1 , Hiroko Nagafuchi1 , Ichiaki Ito2 , Koichi Hirota1 , Michiteru Yoshida2 , Shoichi Ozaki1

  • Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan
  • Department of Biological Science and Technology, Science University of Tokyo, 2641 Yamazaki, Noda 278-8510, Japan
Received:

8 October 2008

Accepted:

26 December 2008

Published online:

13 February 2009

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Abstract

The high mobility group box 1 (HMGB1) protein is a non-histone chromosomal protein that acts as a potent proinflammatory cytokine when actively secreted from LPS- or TNF-activated macrophages, monocytes, and other cells. Anti-HMGB1/2 antibodies have been previously identified in sera from a high proportion of patients with autoimmune diseases. In this study, we examined anti-HMGB1 antibody titers in sera of patients with systemic rheumatic diseases and the correlations between the presence of anti-HMGB1 antibodies and disease activity in systemic lupus erythematosus (SLE) patients by enzyme-linked immunosorbent assay and western blotting. We detected increases in both the levels and the frequency of anti-HMGB1 antibodies in sera from SLE and polymyositis/dermatomyositis (PM/DM) patients, and observed that the presence of anti-HMGB1 antibodies positively correlates with SLE disease activity index. Through epitope mapping, we found that multiple HMGB1 epitopes were recognised in SLE sera, with the major epitope mapping to box A. Another epitope, the joiner region of HMGB1, was preferentially recognized by SLE sera, but not by PM/DM sera. Collectively, these observations suggest that the presence of anti-HMGB1 antibodies correlates with disease activity in SLE patients.

Key words

High mobility group box 1 (HMGB1) - Systemic lupus erythematosus (SLE) - Autoantibody - Epitope - Molecular mimicry