Hayashi Ayako, Nagafuchi Hiroko, Ito Ichiaki, Hirota Koichi, Yoshida Michiteru, Ozaki Shoichi
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
Mod Rheumatol. 2009;19(3):283-92. doi: 10.1007/s10165-009-0151-7. Epub 2009 Feb 13.
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.
高迁移率族蛋白B1（HMGB1）是一种非组蛋白染色体蛋白，当它从脂多糖（LPS）或肿瘤坏死因子（TNF）激活的巨噬细胞、单核细胞及其他细胞中被主动分泌时，可作为一种强效促炎细胞因子发挥作用。此前在高比例自身免疫性疾病患者的血清中已鉴定出抗HMGB1/2抗体。在本研究中，我们通过酶联免疫吸附测定法和蛋白质印迹法检测了系统性风湿性疾病患者血清中的抗HMGB1抗体滴度，并研究了系统性红斑狼疮（SLE）患者中抗HMGB1抗体的存在与疾病活动度之间的相关性。我们检测到SLE和多发性肌炎/皮肌炎（PM/DM）患者血清中抗HMGB1抗体的水平和频率均升高，并且观察到抗HMGB1抗体的存在与SLE疾病活动指数呈正相关。通过表位作图，我们发现SLE血清中可识别多个HMGB1表位，主要表位定位于A盒。另一个表位，即HMGB1的连接区，优先被SLE血清识别，但不被PM/DM血清识别。总体而言，这些观察结果表明抗HMGB1抗体的存在与SLE患者的疾病活动度相关。
