Interference of tumor necrosis factor inhibitor treatments on soluble tumor necrosis factor receptor 2 levels in rheumatoid arthritis.
Interference of tumor necrosis factor inhibitor treatments on soluble tumor necrosis factor receptor 2 levels in rheumatoid arthritis.
复制标题
肿瘤坏死因子抑制剂治疗对类风湿性关节炎可溶性肿瘤坏死因子受体 2 水平的干扰。
DOI：
10.1016/j.plabm.2019.e00122
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发表时间：
2019
影响因子：
1.9
通讯作者：
Liao,KatherineP
中科院分区：
文献类型：
--
作者：
Yang,Nicole;Huang,Jie;Frits,Michelle;Iannaccone,Christine;Weinblatt,MichaelE;Rifai,Nader;Shadick,Nancy;Bradwin,Gary;Liao,KatherineP
目的可溶性肿瘤坏死因子受体 II (sTNFR2) 被用作研究不同人群心血管疾病 (CVD) 的生物标志物。 TNF 抑制剂 (TNFi) 是治疗炎症的常见方法。本研究的目的是检查 TNFi 的使用是否影响测量的 sTNFR2 水平。方法我们研究了一组 RA 患者的血液样本的临床数据和高灵敏度 C 反应蛋白 (hsCRP) 测量值。为了评估干扰，我们使用 Pearson 相关性测试了整个队列的 sTNFR2 和 TNFi 之间的预期正相关性。然后，我们对 sTNFR2 和 TNFi 进行 Pearson 相关性分析，并依次删除使用阿达木单抗、依那西普和英夫利昔单抗的受试者；如果发生干扰，则不会观察到 hsCRP 和 sTNFR2 之间的相关性，并且可以通过移除导致干扰的治疗受试者来恢复相关性。结果我们研究了 190 名受试者，其中 84.2% 为女性，73.4% 为抗 CCP 阳性。所有 sTNFR2 水平超过可测量水平的受试者均服用依那西普。在评估整个队列时，没有观察到 hsCRP 和 sTNFR2 之间预期的正相关性，r=0.05，p=0.51。然而，仅在排除服用依那西普（r=0.46，p<0.0001）的受试者以及排除阿达木单抗或英夫利昔单抗的受试者后，预期的相关性才恢复。仅使用依那西普进行 sTNFR2 ELISA，并证明与 sTNFR2 直接结合。结论我们的数据确定了依那西普和 TNFR2 测定之间的干扰。在 TNFi 中，只有依那西普具有模仿 TNFR2 的 TNF 结合结构域。在以依那西普为治疗选择的人群中设计使用 sTNFR2 的研究时，应考虑这些数据。
ObjectiveSoluble Tumor Necrosis Factor Receptor II (sTNFR2) is used as a biomarker to study cardiovascular disease (CVD) in diverse populations. TNF inhibitors (TNFi's) are a common treatment for inflammatory conditions. The objective of this study was to examine whether TNFi use impacts measured sTNFR2 levels.MethodsWe studied blood samples from a cohort of RA patients with clinical data and high sensitivity-C-reactive protein (hsCRP) measurements. To assess for interference, we tested the entire cohort for the expected positive correlation between sTNFR2 and TNFi using Pearson correlations. We then performed Pearson correlations between sTNFR2 and TNFi and sequentially removed subjects on adalimumab, etanercept, and infliximab; if interference was occurring, no correlation would be observed between hsCRP and sTNFR2, and correlation would be restored by removing subjects on the treatment causing the interference.ResultsWe studied 190 subjects, 84.2% female, 73.4% anti-CCP positive. All subjects with sTNFR2 level exceeding measurable level were on etanercept. The expected positive correlation between hsCRP and sTNFR2 was not observed when assessing the entire cohort, r = 0.05, p = 0.51. However, the expected correlation was restored only after excluding subjects on etanercept, r = 0.46, p < 0.0001, and not adalimumab or infliximab. ELISA for sTNFR2 was performed using etanercept only and demonstrated direct binding to sTNFR2.ConclusionsOur data identified interference between etanercept and the TNFR2 assay. Of the TNFi's, only etanercept has a TNF-binding domain modeled after TNFR2. These data should be considered when designing studies using sTNFR2 in populations where etanercept is a treatment option.