Pullerits R, Bokarewa M, Dahlberg L, Tarkowski A
Department of Rheumatology and Inflammation Research, University of Göteborg, Göteborgrille, Sweden.
Rheumatology (Oxford). 2007 Aug;46(8):1367-71. doi: 10.1093/rheumatology/kem141. Epub 2007 Jun 14.
The receptor for advanced glycation end products (RAGE) is expressed by many cells in joints of rheumatoid arthritis (RA) patients and interacts with a variety of pro-inflammatory ligands that are enriched in inflamed joint. The RAGE-ligand interaction leads to a sustained inflammatory response. Also, secreted form of the receptor, called soluble RAGE (sRAGE), the levels of which are decreased in RA patients, modulates inflammatory responses. We sought to determine whether RA patients display increased occurrence of autoantibodies against RAGE and whether such an autoantibody production is related to disease characteristics.
Matching samples of blood and synovial fluid were collected from 50 patients with RA with acute joint effusion. Blood from 43 healthy individuals and synovial fluid samples from 32 patients with non-inflammatory joint diseases were used for comparison. Anti-RAGE antibody levels were analysed using an ELISA.
RA patients displayed significantly higher blood and synovial fluid levels of anti-RAGE antibodies, both of IgG as well as of IgM class as compared with healthy controls and with patients with non-inflammatory joint diseases. Patients with seropositive RA had significantly less IgG antibodies in their synovial fluid as compared to seronegative patients. Furthermore, the presence of IgG class of anti-RAGE antibodies locally in the joint was found to be related to less aggressive, i.e. non-erosive disease.
These results suggest that RAGE-specific B cell response protect patients with RA from destructive course of the disease.
晚期糖基化终末产物受体（RAGE）在类风湿关节炎（RA）患者关节的许多细胞中表达，并与多种在炎症关节中富集的促炎配体相互作用。RAGE-配体相互作用导致持续的炎症反应。此外，受体的分泌形式，即可溶性RAGE（sRAGE），其水平在RA患者中降低，可调节炎症反应。我们试图确定RA患者是否表现出针对RAGE的自身抗体发生率增加，以及这种自身抗体的产生是否与疾病特征有关。
从50例有急性关节积液的RA患者中采集配对的血液和滑液样本。使用43名健康个体的血液和32例非炎症性关节疾病患者的滑液样本进行比较。使用酶联免疫吸附测定法（ELISA）分析抗RAGE抗体水平。
与健康对照和非炎症性关节疾病患者相比，RA患者血液和滑液中抗RAGE抗体的IgG和IgM类水平均显著更高。血清阳性RA患者的滑液中IgG抗体明显少于血清阴性患者。此外，发现关节局部存在IgG类抗RAGE抗体与侵袭性较小即非侵蚀性疾病有关。
这些结果表明，RAGE特异性B细胞反应可保护RA患者免受疾病的破坏性进程。
