Decreased levels of soluble receptor for advanced glycation end products in patients with rheumatoid arthritis indicating deficient inflammatory control.

Decreased levels of soluble receptor for advanced glycation end products in patients with rheumatoid arthritis indicating deficient inflammatory control.
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DOI:
10.1186/ar1749
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发表时间:
2005
影响因子:
4.9
通讯作者:
Tarkowski A
Tarkowski A
中科院分区:
医学2区
文献类型:
--
作者:
Pullerits R;Bokarewa M;Dahlberg L;Tarkowski A

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晚期糖基化终产物受体(RAGE)是免疫球蛋白超家族的成员,以细胞表面分子的形式表达,与多种配体结合。其中一个配体是高迁移率族盒染色体蛋白1,它是一种有效的促炎细胞因子,在类风湿关节炎(RA)患者的滑膜组织和滑液中表达增加。高迁移率族盒染色体蛋白1与细胞表面RAGE的相互作用导致炎症反应。相反,可溶性RAGE(SRAGE)的存在可能会取消细胞激活,因为配体是在与表面受体相互作用之前结合的。我们的目的是分析SRAGE在慢性关节炎症(RA)患者中的存在程度,并与非炎症性关节疾病患者和健康受试者进行比较,并评估SRAGE水平与疾病特征之间是否存在关联。采集62例RA急性关节积液患者的血液和滑液配对标本。以45例健康人的血液、33例非炎症性关节疾病患者的滑液标本和6例非炎症性关节疾病患者的血液为对照。用双抗体夹心法分析血清sRAGE水平。RA患者血清sRAGE水平(871±66pg/ml,P<0.0001)显著低于正常对照组(1290±78pg/ml)和非炎症性关节疾病患者(1569±168pg/ml)。RA患者滑液中sRAGE水平(379±36pg/ml)低于相应的血液标本,且与血sRAGE显著相关。有趣的是,与未接受抗风湿治疗的RA患者相比,接受甲氨蝶呤治疗的RA患者的滑液中sRAGE水平显著升高。我们的结论是,RA患者的sRAGE水平降低可能会增加炎症的倾向,而甲氨蝶呤的治疗则抵消了这一特征。
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily being expressed as a cell surface molecule and binding a variety of ligands. One of these ligands is high-mobility group box chromosomal protein 1, a potent proinflammatory cytokine, expression of which is increased in synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The interaction of high-mobility group box chromosomal protein 1 with cell-surface RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) may abrogate cellular activation since the ligand is bound prior to interaction with the surface receptor. Our aim was to analyse to what extent sRAGE is present in patients with chronic joint inflammation (RA) as compared with patients with non-inflammatory joint disease and with healthy subjects, and to assess whether there is an association between sRAGE levels and disease characteristics. Matching samples of blood and synovial fluid were collected from 62 patients with RA with acute joint effusion. Blood from 45 healthy individuals, synovial fluid samples from 33 patients with non-inflammatory joint diseases and blood from six patients with non-inflammatory joint diseases were used for comparison. sRAGE levels were analysed using an ELISA. RA patients displayed significantly decreased blood levels of sRAGE (871 ± 66 pg/ml, P < 0.0001) as compared with healthy controls (1290 ± 78 pg/ml) and with patients with non-inflammatory joint disease (1569 ± 168 pg/ml). Importantly, sRAGE levels in the synovial fluid of RA patients (379 ± 36 pg/ml) were lower than in corresponding blood samples and correlated significantly with blood sRAGE. Interestingly, a significantly higher sRAGE level was found in synovial fluid of RA patients treated with methotrexate as compared with patients without disease-modifying anti-rheumatic treatment. We conclude that a decreased level of sRAGE in patients with RA might increase the propensity towards inflammation, whereas treatment with methotrexate counteracts this feature.
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发表时间: 2002-05-01
影响因子: 13.6
作者:
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发表时间: 2002-05-01
期刊: GENES AND IMMUNITY
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发表时间: 1999-08-25
期刊: MOLECULAR BRAIN RESEARCH
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发表时间: 1997-07-01
影响因子: 3.6
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Renard, C;Chappey, O;Wautier, JL
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DOI: 10.1002/art.11028
发表时间: 2003-06-01
影响因子: --
作者:
Pullerits, R;Jonsson, IM;Tarkowski, A
通讯作者: Tarkowski, A