Increased bioactive TNF in human systemic lupus erythematosus:: associations with cell death
Increased bioactive TNF in human systemic lupus erythematosus:: associations with cell death
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DOI：
10.1191/0961203302lu160oa
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发表时间：
2002-01-01
期刊：
影响因子：
2.6
通讯作者：
Graninger, WB
中科院分区：
文献类型：
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作者：
Aringer, M;Feierl, E;Graninger, WB
在系统性红斑狼疮（SLE）中，血清TNF升高，并且与其可溶性受体和疾病活动性相关。因此，我们研究了（i）SLE血清中的TNF是否具有生物活性，（ii）SLE细胞是否对TNF反应，以及（iii）是否与细胞死亡相关，这被认为是SLE的致病因素。活动性SLE患者血清诱导成纤维细胞CD 54增加，这是取消了对TNF的阻断抗体，表明TNF的生物活性。SLE淋巴细胞表面TNF-RI的表达与健康淋巴细胞相似，TNF-RII的表达略有增加。重组TNF诱导SLE患者PBMC中的细胞死亡，提示功能性受体。血清sTNF-RII水平（作为TNF活性的替代标志物）与sTNF-RI和疾病活动相关，正如预期的那样，也与死亡淋巴细胞的百分比和淋巴细胞CD 95相关。SLE血清含有增加量的生物活性TNF。SLE患者外周血淋巴细胞表达功能性TNF受体。最后，与细胞死亡和CD 95受体的关联表明TNF可能是SLE的致病因素。
In systemic lupus erythematosus (SLE) serum TNF is increased and correlates with its soluble receptors and with disease activity. We therefore investigated (i) whether the TNF in SLE serum is bioactive, (ii) whether SLE cells react to TNF and (iii) whether there are associations with cell death, which is regarded as pathogenic in SLE. Sera from active SLE patients induced an increase in fibroblast CD54, which was abolished by blocking antibodies against TNF, suggesting TNF bioactivity. SLE lymphocytes had a similar surface expression of TNF-RI as healthy lymphocytes, their expression of TNF-RII was slightly increased. Recombinant TNF induced cell death in PBMC of SLE patients, suggesting functional receptors. Serum levels of sTNF-RII (as a surrogate marker for TNF activity) correlated with sTNF-RI and disease activity, as expected, and also correlated with the percentage of dying lymphocytes and with lymphocytic CD95. SLE sera contain increased amounts of biologically active TNF. Peripheral blood lymphocytes of SLE patients express functional TNF receptors. Finally, associations with cell death and CD95 receptors suggest that TNF may be pathogenic in SLE.