High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus.
High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus.
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DOI：
10.1186/ar3332
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发表时间：
2011-05-06
影响因子：
4.9
通讯作者：
Bijl M
中科院分区：
文献类型：
--
作者：
Abdulahad DA;Westra J;Bijzet J;Limburg PC;Kallenberg CG;Bijl M
高迁移率族蛋白1(HMGB1)是一种核内非组蛋白。HMGB1由炎性细胞分泌，从凋亡和坏死细胞中被动释放，可能是一种促炎介质。随着凋亡细胞在系统性红斑狼疮(SLE)中的积聚，SLE患者HMGB1水平可能升高。HMGB1也可能作为自身抗原，导致产生抗HMGB1抗体。本研究测定了SLE患者血清HMGB1和抗-HMGB1水平，并与健康对照组(HC)进行比较，分析其与疾病活动性的关系。研究人群包括70名SLE患者和35名年龄和性别匹配的HC。33例SLE患者为静止期疾病，37例为活动期患者。其中19人患有狼疮性肾炎。用免疫印迹和酶联免疫吸附试验检测HMGB1水平。用双抗体夹心法检测血清抗HMGB1抗体水平。临床和血清学指标按常规程序进行评估。SLE患者的HMGB1水平仅通过Western blotting才能可靠地测量，且与HC相比显著升高。在活动性疾病期间，HMGB1水平升高，特别是在肾脏受累的患者。血清HMGB1水平与SLEDAI、蛋白尿、抗双链DNA水平相关，与补体C3呈负相关。SLE患者抗-HMGB1水平显著高于HC，且与HMGB1水平呈正相关。系统性红斑狼疮患者，尤其是活动性肾病患者血清中HMGB1水平升高。血清HMGB1水平与SLEDAI评分、蛋白尿以及抗HMGB1抗体水平有关。这些发现表明，除HMGB1外，HMGB1-抗HMGB1免疫复合物在SLE的发病机制中也起作用，特别是在有肾脏损害的患者中。
High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein. HMGB1, which is secreted by inflammatory cells and passively released from apoptotic and necrotic cells, may act as a pro-inflammatory mediator. As apoptotic cells accumulate in systemic lupus erythematosus (SLE), HMGB1 levels might be increased in SLE. HMGB1 may also serve as an autoantigen, leading to the production of anti-HMGB1 antibodies. In this study we determined levels of HMGB1 and anti-HMGB1 in SLE patients in comparison to healthy controls (HC) and analysed their relation with disease activity. The study population consisted of 70 SLE patients and 35 age- and sex-matched HC. Thirty-three SLE patients had quiescent disease, the other 37 patients were selected for having active disease. Nineteen of these had lupus nephritis. HMGB1 levels were measured with both Western blot and ELISA. Anti-HMGB1 levels were measured by ELISA. Clinical and serological parameters were assessed according to routine procedures. HMGB1 levels in SLE patients could be measured reliably by Western blotting only, and were significantly increased compared to HC. During active disease HMGB1 levels increased, in particular in patients with renal involvement. Serum HMGB1 levels correlated with SLEDAI, proteinuria, and anti-dsDNA levels, and showed a negative correlation with complement C3. Anti-HMGB1 levels were significantly increased in SLE patients compared to HC, and positively correlated with HMGB1 levels. Levels of HMGB1 in the sera of SLE patients, in particular in those with active renal disease, are increased. Serum HMGB1 levels are related to SLEDAI scores and proteinuria, as well as to levels of anti-HMGB1 antibodies. These findings suggest that besides HMGB1, HMGB1-anti-HMGB1 immune complexes play a role in the pathogenesis of SLE, in particular in patients with renal involvement.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Pisetsky, David S.
影响因子：
5.5
作者：
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通讯作者：
Harris, Helena Erlandsson