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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 283-292 |
| Number of pages | 10 |
| Journal | Modern Rheumatology |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 13 2009 |
| Externally published | Yes |
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Keywords
- Autoantibody
- Epitope
- High mobility group box 1 (HMGB1)
- Molecular mimicry
- Systemic lupus erythematosus (SLE)
ASJC Scopus subject areas
- Rheumatology
Cite this
Lupus antibodies to the HMGB1 chromosomal protein : Epitope mapping and association with disease activity. / Hayashi, Ayako; Nagafuchi, Hiroko; Ito, Ichiaki; Hirota, Koichi; Yoshida, Michiteru; Ozaki, Shoichi.
In: Modern Rheumatology, Vol. 19, No. 3, 13.02.2009, p. 283-292.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lupus antibodies to the HMGB1 chromosomal protein
T2 - Epitope mapping and association with disease activity
AU - Hayashi, Ayako
AU - Nagafuchi, Hiroko
AU - Ito, Ichiaki
AU - Hirota, Koichi
AU - Yoshida, Michiteru
AU - Ozaki, Shoichi
PY - 2009/2/13
Y1 - 2009/2/13
N2 - 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.
AB - 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.
KW - Autoantibody
KW - Epitope
KW - High mobility group box 1 (HMGB1)
KW - Molecular mimicry
KW - Systemic lupus erythematosus (SLE)
UR - http://www.scopus.com/inward/record.url?scp=67349282299&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349282299&partnerID=8YFLogxK
U2 - 10.1007/s10165-009-0151-7
DO - 10.1007/s10165-009-0151-7
M3 - Article
C2 - 19214652
AN - SCOPUS:67349282299
VL - 19
SP - 283
EP - 292
JO - Modern Rheumatology
JF - Modern Rheumatology
SN - 1439-7595
IS - 3
ER -