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神经营养因子及其受体在脊柱关节炎滑膜炎中的作用:与炎症及治疗反应的关系

Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment.

作者信息

Rihl M, Kruithof E, Barthel C, De Keyser F, Veys E M, Zeidler H, Yu D T Y, Kuipers J G, Baeten D

机构信息

Hannover Medical School (MHH), Department of Rheumatology (OE 6850), Carl-Neuberg-Str 1, 30625 Hannover, Germany.

出版信息

Ann Rheum Dis. 2005 Nov;64(11):1542-9. doi: 10.1136/ard.2004.032599. Epub 2005 Apr 7.

Abstract

OBJECTIVE

To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA).

MATERIAL AND METHODS

Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor alpha antibody, infliximab.

RESULTS

mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment.

CONCLUSIONS

NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.

摘要

目的

研究神经营养因子(NT)家族的四个成员及其四种相应受体的表达是否与脊柱关节炎(SpA)患者的滑膜炎症相关。

材料与方法

采用酶联免疫吸附测定法(ELISA)检测滑液(SF)和血清中的NTs及其受体。对SpA、类风湿关节炎和骨关节炎(OA)患者的滑膜组织活检标本进行免疫组织化学检测。在SpA滑膜中,还评估了用单克隆抗肿瘤坏死因子α抗体英夫利昔单抗治疗12周前后受体trkA和NGFRp75的免疫反应性。

结果

所有NTs和受体的mRNA转录本均在炎症滑膜中表达。在蛋白水平上,SpA患者滑液中的脑源性神经营养因子和NT-3显著高于OA患者。相比之下,血清样本的ELISA检测显示,SpA中含量最高的成员是NT-4。免疫组织化学显示,NT受体trkA和NGFRp75在SpA患者的炎症滑膜中高表达,分别与血管形成和淋巴聚集相关。此外,英夫利昔单抗治疗后两种受体的免疫反应性均显著降低。

结论

NTs及其受体在SpA患者的炎症外周关节中表达。它们的表达并非固有性的,而是与炎症相关,可能参与了局部疾病过程。

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