Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A
Systemic cytokine levels and the effects of etanercept in TNF receptor-associated periodic syndrome (TRAPS) involving a C33Y mutation in TNFRSF1A
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DOI：
10.1093/rheumatology/kei090
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发表时间：
2006-01-01
期刊：
影响因子：
5.5
通讯作者：
Todd, I
中科院分区：
文献类型：
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作者：
Nowlan, ML;Drewe, E;Todd, I
Objective.研究TNF受体相关周期综合征（TRAPS）患者血浆中促炎细胞因子IL-6、TNF-α、IL-1 β、IL-8、IL-10和IL-12 p70水平与CRP水平和依那西普治疗的关系。使用细胞因子微珠阵列，在从TNFRSF 1A中具有C33 Y突变并诊断为TRAPS的8名患者获得的连续血浆样品中测量细胞因子浓度。将TRAPS样本与正常对照和类风湿关节炎患者的样本进行比较。IL-6水平在C33 Y TRAPS患者中显著升高，并且在一些患者中这些与CRP水平相关。TRAPS患者的IL-8水平也显著升高。然而，TNF-α和IL-1 β都没有表现出类似的增加。这与类风湿性关节炎患者不同，类风湿性关节炎患者的IL-6、IL-8、TNF-α、IL-1 β和IL-10水平显著升高。TRAPS患者血浆中可检测的TNF-α水平在依那西普治疗期间升高。C33 Y TRAPS的细胞因子谱不同于典型的自身免疫炎性病症如类风湿性关节炎的细胞因子谱，因为在C33 Y TRAPS患者中仅IL-6和IL-8升高，与促炎细胞因子的普遍升高不同。然而，只有一些C33 Y患者的测试显示升高的IL-6和CRP之间的关系。这与临床观察结果一致，即TRAPS个体之间存在显著异质性，包括同一家族队列中的个体。虽然依那西普对某些TRAPS患者有治疗作用，但它可能通过增加TNF-α的稳定性诱导TNF-α的血浆浓度增加。
Objective. To investigate the levels of the pro-inflammatory cytokines IL-6, TNF-alpha, IL-1 beta, IL-8, IL-10 and IL-12p70 in the plasma of patients with TNF receptor-associated periodic syndrome (TRAPS) in relation to CRP levels and treatment with etanercept.Methods. Cytokine concentrations were measured in sequential plasma samples obtained from eight patients with a C33Y mutation in TNFRSF1A and diagnosed with TRAPS, using cytokine bead array. The TRAPS samples were compared with samples from normal controls and rheumatoid arthritis patients.Results. Levels of IL-6 were significantly elevated in C33Y TRAPS patients and these correlated with CRP levels in some of the patients. IL-8 levels were also significantly elevated in the TRAPS patients. However, neither TNF-alpha nor IL-1 beta demonstrated a similar increase. This differed from the patients with rheumatoid arthritis, for whom levels of IL-6, IL-8, TNF-alpha, IL-1 beta and IL-10 were significantly elevated. The levels of detectable TNF-alpha in the TRAPS patients' plasma were elevated during etanercept treatment.Conclusions. The cytokine profile of C33Y TRAPS differs from that of a typical autoimmune inflammatory condition such as rheumatoid arthritis, as only IL-6 and IL-8 were elevated in C33Y TRAPS patients, as distinct from a generalized elevation of pro-inflammatory cytokines. However, only some of the C33Y patients tested showed a relationship between elevated IL-6 and CRP. This is consistent with clinical observations that there is marked heterogeneity between individuals with TRAPS, including those in the same family cohort. Although etanercept has a therapeutic effect in some TRAPS patients, it induces increased plasma concentrations of TNF-alpha, possibly by increasing TNF-alpha stability.