Spronk P E, Bootsma H, Huitema M G, Limburg P C, Kallenberg C G
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Clin Exp Immunol. 1994 Sep;97(3):439-44. doi: 10.1111/j.1365-2249.1994.tb06107.x.
Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.
活动性系统性红斑狼疮（SLE）的特征是在许多器官中出现免疫沉积物及随后的血管炎症。黏附分子的表达及上调是炎症细胞迁移至组织的基础。最近，已描述了这些分子的可溶性异构体，它们可能是其在组织中上调的一种表现，因此也是疾病活动的表现。本研究的目的是评估可溶性黏附分子水平的变化是否反映疾病活动。我们分析了连续22次SLE病情加重前6个月内的系列血清，检测可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性细胞间黏附分子-1（sICAM-1）和sE-选择素的水平。这些水平与临床疾病活动度（SLEDAI）、抗双链DNA水平及补体水平相关。在疾病活动度最高时，SLE患者的sVCAM-1水平高于对照组（P<0.0001），有肾脏受累的患者水平高于无肾脏受累者（P<0.02）。sVCAM-1水平与SLEDAI评分相关（P<0.05），与C3水平呈负相关（P=0.01）。此外，在存在抗双链DNA的情况下，sVCAM-1水平倾向于与这些自身抗体水平相关（P<0.1）。sICAM-1水平正常，与对照组相比，sE-选择素水平甚至下降。复发时sVCAM-1水平高于该时间点前6个月（P=0.001）。这种升高与SLEDAI评分的升高相关（P<0.02）。在所有研究的病情加重中，sICAM-1和sE-选择素水平未升高，仍处于正常范围。总之，与sICAM-1和sE-选择素不同，sVCAM-1水平升高，在SLE病情加重期间与疾病活动度平行升高，并与补体因子水平降低相关。这支持了免疫沉积物形成、补体级联激活和内皮细胞激活的假说。血管黏附分子的同时上调可能导致活化的炎症细胞迁移，从而诱导组织损伤。
