CORRELATION BETWEEN SERUM LEVELS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR AND DISEASE-ACTIVITY IN SYSTEMIC LUPUS-ERYTHEMATOSUS
CORRELATION BETWEEN SERUM LEVELS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR AND DISEASE-ACTIVITY IN SYSTEMIC LUPUS-ERYTHEMATOSUS
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DOI：
10.1002/art.1780360812
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发表时间：
1993-08-01
影响因子：
--
通讯作者：
WALLACH, D
中科院分区：
文献类型：
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作者：
ADERKA, D;WYSENBEEK, A;WALLACH, D
目的：确定血清可溶性肿瘤坏死因子受体（sTNFR）的检测值在监测系统性红斑狼疮（SLE）疾病活动度方面相较于已确定的参数（如抗双链DNA）的价值，并确定血清sTNFR是否具有生物活性以及能否有效抑制肿瘤坏死因子（TNF）的生物活性。
方法：在一项前瞻性队列研究中，纳入53例连续的门诊或住院SLE患者以及140例连续的健康受试者。使用针对sTNFR的小鼠单克隆抗体和兔抗血清，通过独特的双面捕获酶联免疫吸附测定法测量血清sTNFR水平。
结果：在46例SLE患者组中，p55（I型）和p75（II型）可溶性受体的平均±标准差浓度均显著高于对照组：分别为1.89±0.89纳克/毫升对0.77±0.19纳克/毫升以及7.25±3.89纳克/毫升对3.02±0.57纳克/毫升（两者均P<0.0001）。健康受试者和这些患者（以及另外7例进行了序贯研究的患者）中升高的发生率和程度与疾病活动度的相关性比血清抗DNA抗体的出现更强（p55和p75 sTNFR与疾病活动度的相关系数分别为0.81和0.85，抗DNA抗体为0.51）。sTNFR水平的升高似乎主要反映了其生成增加，而在较小程度上是由于肾功能损害导致的清除减少。SLE患者的血清对TNF的体外细胞毒活性有显著的抑制作用，并且这被证明完全是由于其较高的sTNFR受体浓度所致。
结论：血清sTNFR水平的升高可能成为SLE活动度的一个有用标志物，因为它比目前日常临床环境中使用的任何其他实验室或临床参数都具有更强的相关性。在SLE患者血清中达到的浓度下，sTNFR有效地抑制了TNF的生物活性，因此可能是SLE表现强度的一个重要决定因素。
Objective. To determine the value of measurement of serum soluble tumor necrosis factor receptor (sTNFR), compared with established parameters such as anti-double-stranded DNA, in monitoring systemic lupus erythematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity.Methods. Fifty-three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort study. Serum levels of sTNFR were measured by a unique 2-sided capture enzyme-linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR.Results, The mean +/- SD concentrations of both the p55 (type I) and p75 (type II) soluble receptors were significantly higher in a group of 46 SLE patients than in controls: 1.89 +/- 0.89 ng/ml versus 0.77 +/- 0.19 ng/ml and 7.25 +/- 3.89 ng/ml versus 3.02 +/- 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects and these patients (as well as in 7 additional patients on whom sequential studies were performed) correlated with disease activity more than did the occurrence of serum anti-DNA antibodies (correlation coefficients with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respectively, and 0.51 for anti-DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor extent, reduced clearance due to impairment of renal function. Sera of the SLE patients had a marked inhibitory effect on the in vitro cytocidal activity of TNF, and this was shown to result entirely from their higher sTNFR receptor concentration.Conclusion. An increase in serum levels of sTNFR may become a useful marker for SLE activity since it shows a stronger correlation than do any other laboratory or clinical parameters employed presently in the daily clinical setting. At the concentrations attained in the serum of SLE patients, sTNFR effectively inhibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.