Stegeman C A, Tervaert J W, Huitema M G, Kallenberg C G
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Clin Exp Immunol. 1993 Mar;91(3):415-20. doi: 10.1111/j.1365-2249.1993.tb05918.x.
Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.
采用夹心酶联免疫吸附测定法(ELISA)检测了16例经组织学证实有18次韦格纳肉芽肿(WG)复发的患者系列血清样本中可溶性白细胞介素-2受体(sIL-2R)、可溶性CD4(sCD4)和CD8(sCD8)水平,作为T细胞活化的标志物。全组患者复发前6个月sIL-2R水平从1065 U/ml(中位数,范围373 - 2345 U/ml)升至复发时的1684 U/ml(中位数,范围486 - 3404 U/ml)(P = 0.10)。8次主要复发显示sIL-2R水平显著升高,从复发前6个月的1008 U/ml(中位数,范围686 - 1553 U/ml)升至复发时的1994 U/ml(中位数,范围1469 - 3404 U/ml)(P < 0.01)。8次主要复发时的sIL-2R水平显著高于10次轻微复发时的水平(P < 0.05)。轻微复发时sIL-2R水平无显著升高。复发前6个月期间,15/18例患者抗中性粒细胞胞浆抗体(ANCA)滴度升高两个或更多滴度级,或从阴性转为阳性。在所有7例ANCA滴度升高且sIL-2R水平至少升高25%的病例中,ANCA滴度升高比sIL-2R升高至少提前1个月。复发时sIL-2R水平与C反应蛋白水平相关(r = 0.488,P < 0.05),与疾病活动评分相关(r = 0.824,P < 0.002)。sCD4或sCD8水平无显著变化,尽管主要复发时sCD4水平有升高趋势。我们得出结论,韦格纳肉芽肿的主要复发伴有全身性T细胞活化。然而,T细胞活化似乎并不先于ANCA滴度升高。