抗体芯片在类风湿关节炎患者滑液与血浆蛋白检测中的应用

Protein expression profile in synovial fluid and plasma from patients with rheumatoid arthritis using antibody microarrays

目的应用抗体芯片研究类风湿关节炎(rheumatoid arthritis,RA)患者滑液与血浆蛋白表达谱的差异。方法选取3例RA患者的血浆和滑液标本,用抗体芯片试剂盒同时检测507种蛋白质的表达,筛选配对滑液与血浆差异表达的蛋白(差异>2.0倍)。结果筛选出67种在RA滑液中明显高表达的蛋白质,其中10种为新发现的滑液蛋白,包括IL-28A、成纤维细胞生长因子(fibroblast growth factor,FGF)-6、FGF-结合蛋白(FGF-binding protein,FGF-BP)、血管生成素(angiopoietin)4、刺鼠相关蛋白(agouti-related protein,AgRP)、食欲素(orexin)A、抵抗素样分子(resistin-like molecule,RELM)-β、肾母细胞瘤过度表达基因(nephroblastoma overexpressed,NOV)/CCN3、生长分化因子相关血清蛋白(growth and differentiation factor-associated serum protein,GASP)-2/WFIKKN、膜卷曲相关蛋白(membrane frizzled-related protein,MFRP)。芯片分析未显示滑液中低表达的蛋白质。结论揭示RA患者滑液蛋白质表达谱的特点可以为研究RA滑膜炎和(或)骨破坏的发生机制提供新的线索。

Objective To identify differences of protein expression profile between synovial fluid and plasma in patients with rheumatoid arthritis （RA）. Methods Paired plasma and synovial fluid samples from 3 patients with RA were analyzed for 507 human proteins by antibody microarrays A standard 〉 2.0-fold cutoff value was used to determine differentially expressed proteins. Results The array analysis showed that the expression levels of 67 proteins were increased in RA synovial fluid compared with paired plasma. Ten of those proteins were not previously found in synovial fluid or synovium of RA, including IL- 28A, fibroblast growth factor （FGF）-6, FGF-binding protein （FGF-BP）, angiopoietin-4, agouti-related protein （AgRP）, orexin A, resistin-like molecule （RELM）-β, nephroblastoma overexpressed （NOV）/ CCN3, growth and differentiation factor-associated serum protein （GASP）-2/WFIKKN, and membrane frizzled-related protein （MFRP）. Conclusion This study provides insights into the nature of synovial fluid protein profile in RA patients and suggests new targets for studying the involvement of proteins in synovitis and/or bone damage.