PDF(Pubmed)
Abstract：
BACKGROUND: Fibroblast-like synoviocytes (FLS) play a critical role in inflammation that contributes to disease progression in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis (RA), FLS express tumor necrosis factor alpha (TNFα). TNFα signaling has been shown to be upstream of transforming growth factor beta (TGFβ) signaling. Overexpression of TNFα and TGFβ, as well as related proteins, can cause increased inflammation in RA. In this study, we examine the effects of inhibiting TNFα signaling with adalimumab on FLS isolated from synovial fluid of patients with JIA.
METHODS: Synovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24 h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols.
RESULTS: In persistent FLS, TNFα (fold change [FC] = 1.2 p = 0.001), TGFβ (FC = 1.5 p = 0.001), lymphotoxin alpha (LTα) (FC = 4.3 p = 0.015), soluble tumor necrosis factor receptor 1 (sTNFRI) (FC = 5.1 p = 0.008), and soluble tumor necrosis factor receptor 2 (sTNFRII) (FC = 3.8 p = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNFα was significantly elevated (FC = 1.04 p = 0.023) while TGFβ (FC = 1.03 p = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells.
CONCLUSIONS: This data suggests that, after only 24 h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNFα signaling in extended-to-be fibroblast-like synoviocytes.
METHODS: Synovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24 h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols.
RESULTS: In persistent FLS, TNFα (fold change [FC] = 1.2 p = 0.001), TGFβ (FC = 1.5 p = 0.001), lymphotoxin alpha (LTα) (FC = 4.3 p = 0.015), soluble tumor necrosis factor receptor 1 (sTNFRI) (FC = 5.1 p = 0.008), and soluble tumor necrosis factor receptor 2 (sTNFRII) (FC = 3.8 p = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNFα was significantly elevated (FC = 1.04 p = 0.023) while TGFβ (FC = 1.03 p = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells.
CONCLUSIONS: This data suggests that, after only 24 h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNFα signaling in extended-to-be fibroblast-like synoviocytes.
摘要：
背景：成纤维细胞样滑膜细胞（FLS）在炎症中起关键作用，这有助于幼年特发性关节炎（JIA）的疾病进展。在类风湿性关节炎（RA）中，FLS表达肿瘤坏死因子α(TNFα)。TNFα信号传导已显示为转化生长因子β(TGFβ)信号传导的上游。TNFα和TGFβ的过表达,以及相关的蛋白质，可导致RA的炎症增加。在这项研究中,我们研究了阿达木单抗抑制TNFα信号对JIA患者滑液中分离出的FLS的作用.
方法：从我们库的41名患者中选择滑液样本。在这些样本中，23例诊断为持续性少关节JIA，18例诊断为扩展少关节JIA。所有样本都是在患者延伸到多关节病程之前采集的，或者我们所谓的扩展未来(ETB)，并且仅在关节穿刺术时不使用药物或非甾体类抗炎药（NSAIDs）。对于细胞研究，FLS从滑液中分离并用阿达木单抗处理24小时。根据他们的协议。
结果：在持久性FLS中，TNFα（倍数变化[FC]=1.2p=0.001），TGFβ（FC=1.5p=0.001），淋巴毒素α（LTα）（FC=4.3p=0.015），可溶性肿瘤坏死因子受体1（sTNFRI）（FC=5.1p=0.008），和可溶性肿瘤坏死因子受体2（sTNFRII）（FC=3.8p=0.025）在阿达木单抗处理的细胞中与未处理的细胞相比显着升高。在ETBFLS中，与未处理的细胞相比,在阿达木单抗处理的细胞中TNFα显著升高(FC=1.04p=0.023),而TGFβ(FC=1.03p=0.037)显著降低。
结论：这些数据表明，仅仅24小时后，阿达木单抗可有效减少在延长成纤维细胞样滑膜细胞中初始TNFα信号传导下游发生的炎症。
方法：从我们库的41名患者中选择滑液样本。在这些样本中，23例诊断为持续性少关节JIA，18例诊断为扩展少关节JIA。所有样本都是在患者延伸到多关节病程之前采集的，或者我们所谓的扩展未来(ETB)，并且仅在关节穿刺术时不使用药物或非甾体类抗炎药（NSAIDs）。对于细胞研究，FLS从滑液中分离并用阿达木单抗处理24小时。根据他们的协议。
结果：在持久性FLS中，TNFα（倍数变化[FC]=1.2p=0.001），TGFβ（FC=1.5p=0.001），淋巴毒素α（LTα）（FC=4.3p=0.015），可溶性肿瘤坏死因子受体1（sTNFRI）（FC=5.1p=0.008），和可溶性肿瘤坏死因子受体2（sTNFRII）（FC=3.8p=0.025）在阿达木单抗处理的细胞中与未处理的细胞相比显着升高。在ETBFLS中，与未处理的细胞相比,在阿达木单抗处理的细胞中TNFα显著升高(FC=1.04p=0.023),而TGFβ(FC=1.03p=0.037)显著降低。
结论：这些数据表明，仅仅24小时后，阿达木单抗可有效减少在延长成纤维细胞样滑膜细胞中初始TNFα信号传导下游发生的炎症。
