Expression of human endogenous retrovirus HERV-K18 superantigen is elevated in juvenile rheumatoid arthritis.
Expression of human endogenous retrovirus HERV-K18 superantigen is elevated in juvenile rheumatoid arthritis.
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发表时间：
2005-09
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通讯作者：
Jocelyn Sicat;N. Sutkowski;B. Huber
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作者：
Jocelyn Sicat;N. Sutkowski;B. Huber
目的探讨儿童风湿性疾病中是否存在宿主编码的超抗原。我们测量了在幼年类风湿性关节炎（JRA）和小儿系统性红斑狼疮（SLE）中干扰素-α（IFN-α）诱导人内源性逆转录病毒HERV-K18超抗原的表达和能力。方法采用半定量逆转录-聚合酶链反应（RT-PCR）检测13例JRA患者、11例儿童SLE患者和24例健康对照者外周血或滑液单个核细胞（SFMC）中HERV-K18的表达水平。通过用2000 U/ml预处理样品来测试IFN-α诱导。结果与对照组（平均值0.749，SD 0.598）相比，JRA患者外周血中HERV-K18表达显著升高（HERV-K18与18 S核糖体转录物的平均比值为2.456，SD 2.122; p = 0.014），但SLE患者外周血中HERV-K18表达无显著升高（平均值0.997，SD 0.579; p = 0.258）。7/7例JRA患者SFMC中检测到HERV-K18转录本。IFN-α在JRA（平均诱导倍数= 8.934，SD 15.556）和对照（平均8.270，SD 6.609）中强烈诱导HERV-K18，但在SLE中较弱（平均2.432，SD 2.219; p = 0.009）。发现HERV-K18水平不依赖于先前确定的表达修饰剂，包括EB病毒感染、IFN-α水平或外周血中B细胞的百分比。结论JRA患者血清HERV-K18超抗原水平升高，而SLE患儿血清HERV-K18水平无明显变化，提示JRA患者自身免疫可能是通过超抗原刺激自身反应性T细胞而产生的。
OBJECTIVE To investigate the presence of a host-encoded superantigen as possible etiologic factor in pediatric rheumatic disease. We measured the expression and the ability of interferon-alpha (IFN-alpha) to induce the human endogenous retrovirus HERV-K18 superantigen in juvenile rheumatoid arthritis (JRA) and pediatric systemic lupus erythematosus (SLE). METHODS Expression levels of HERV-K18 were measured in peripheral blood or synovial fluid mononuclear cells (SFMC) from 13 patients with JRA, 11 pediatric SLE patients, and 24 healthy controls, by semiquantitative reverse transcription-polymerase chain reaction, comparing 18S ribosomal transcripts as endogenous standard. IFN-alpha induction was tested by pretreatment of samples with 2000 U/ml. RESULTS HERV-K18 expression was significantly elevated in peripheral blood from patients with JRA (mean ratio of HERV-K18 to 18S ribosomal transcripts 2.456, SD 2.122; p = 0.014), but not patients with SLE (mean 0.997, SD 0.579; p = 0.258), compared to controls (mean 0.749, SD 0.598). HERV-K18 transcripts were detected in SFMC of 7/7 JRA patients. IFN-alpha induced HERV-K18 strongly in JRA (mean fold induction = 8.934, SD 15.556) and controls (mean 8.270, SD 6.609), but weakly in SLE (mean 2.432, SD 2.219; p = 0.009). HERV-K18 levels were found to be independent of previously determined modifiers of expression, including Epstein-Barr virus infection, IFN-alpha levels, or the percentage of B cells in peripheral blood. CONCLUSION HERV-K18 superantigen levels were elevated in JRA patients, but not pediatric patients with SLE, suggesting a possible mechanism for autoimmunity in the former group by superantigen stimulation of autoreactive T cells.