Davas E M, Tsirogianni A, Kappou I, Karamitsos D, Economidou I, Dantis P C
Department of Rheumatology, Evangelismos Hospital, Athens, Greece.
Clin Rheumatol. 1999;18(1):17-22. doi: 10.1007/s100670050045.
The aim of this study was to determine whether the levels of serum cytokines IL-6 and TNFalpha and of the soluble receptors p55 srTNFalpha, p75 srTNFalpha and srIL-2ac are valuable markers of disease activity in patients with systemic lupus erythematosus (SLE) compared with the established parameters of anti-dsDNA, C3, C4 and CH50. Forty patients with SLE, 19 ambulatory and 21 hospitalised, were included in this study. On the day of blood sampling a clinical examination was performed and SLEDAI and ECLAM disease activity scores were used to assess disease activity. Nineteen patients had inactive disease and 21 patients had active disease. Thirteen patients from the second group developed nephritis. In these patients the blood sampling and disease activity assessment were performed twice (at presentation and 6 months after treatment). Serum levels of cytokines and soluble receptors were measured by ELISA. Serum levels of cytokines and soluble receptors of patients with active disease were significantly higher than in patients with inactive disease (IL-6 p = 0.0004, TNFalpha p = 0.0015, srIL-2c p<0.0001, p55 srTNFalpha p<0.0001, p75 srTNFalpha p<0.0001). Serum soluble receptor levels of patients with inactive disease were higher than those of healthy controls (p55 srTNFalpha p<0.0001, p75 srTNFalpha p = 0.0002, srIL-2alpha p = 0.0012). No significant difference was found for TNFalpha and IL-6 (TNFalpha p=0.015, IL-6 p=0.019). Serum TNFalpha levels and especially srIL-2alpha, p55 srTNFalpha( and p75 srTNFalpha levels correlated strongly with SLEDAI and ECLAM disease activity scores, anti-dsDNA, C3, C4 and CH50 (p<0.0001). Serum soluble receptor (srIL-2alphac, p55 srTNFa, p75 srTNFalpha) levels were higher in patients with nephritis before treatment and decreased significantly 6 months after treatment (p=0.005). The same trend was noticed with SLEDAI and ECLAM disease activity scores (p = 0.005) and anti-dsDNA (p = 0.008). In contrast, no significant differences were observed for C3 and C4 levels before and after treatment, which suggests that soluble receptors of cytokines are more sensitive markers of disease activity than C3 or C4 in predicting improvement. Serum levels of srIL-2alpha, p55 srTNFalpha and p75 srTNFalpha could provide useful information about disease activity in SLE patients, especially in cases where the other markers do not.
本研究的目的是确定与抗双链DNA、C3、C4和CH50这些既定参数相比，血清细胞因子白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα）以及可溶性受体p55 srTNFα、p75 srTNFα和srIL-2αc的水平是否为系统性红斑狼疮（SLE）患者疾病活动的有价值标志物。本研究纳入了40例SLE患者，其中19例为门诊患者，21例为住院患者。在采血当天进行了临床检查，并使用SLEDAI和ECLAM疾病活动评分来评估疾病活动度。19例患者疾病无活动，21例患者疾病活动。第二组中的13例患者发生了肾炎。在这些患者中，采血和疾病活动度评估进行了两次（就诊时和治疗后6个月）。通过酶联免疫吸附测定法（ELISA）测量细胞因子和可溶性受体的血清水平。疾病活动患者的细胞因子和可溶性受体血清水平显著高于疾病无活动患者（IL-6 p = 0.0004，TNFα p = 0.0015，srIL-2c p<0.0001，p55 srTNFα p<0.0001，p75 srTNFα p<0.0001）。疾病无活动患者的血清可溶性受体水平高于健康对照者（p55 srTNFα p<0.0001，p75 srTNFα p = 0.0002，srIL-2α p = 0.0012）。未发现TNFα和IL-6有显著差异（TNFα p=0.015，IL-6 p=0.019）。血清TNFα水平，尤其是srIL-2α、p55 srTNFα和p75 srTNFα水平与SLEDAI和ECLAM疾病活动评分、抗双链DNA、C3、C4和CH50密切相关（p<0.0001）。肾炎患者治疗前血清可溶性受体（srIL-2αc、p55 srTNFα、p75 srTNFα）水平较高，治疗后6个月显著下降（p=0.005）。SLEDAI和ECLAM疾病活动评分（p = 0.005）以及抗双链DNA（p = 0.008）也呈现相同趋势。相比之下，治疗前后C3和C4水平未观察到显著差异，这表明在预测病情改善方面，细胞因子的可溶性受体比C3或C4是更敏感的疾病活动标志物。血清srIL-2α、p55 srTNFα和p75 srTNFα水平可为SLE患者的疾病活动提供有用信息，尤其是在其他标志物无法提供信息的情况下。
