Vora A J, Kidd D, Miller D H, Perkin G D, Hughes R A, Ellis B A, Dumonde D C, Brown K A
Department of Immunology, Rayne Institute, UMDS, London, UK.
Mult Scler. 1997 Jun;3(3):171-9. doi: 10.1177/135245859700300301.
This study addressed two questions; first, whether the supranormal adherence of blood lymphocytes from patients with multiple sclerosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-alpha (TNF alpha) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNF alpha and soluble adhesion molecules. In the first part of the investigation, lymphocytes from 14 patients with MS were more adherent to TNF alpha-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5-8 month period, found that changes in binding to TNF alpha-treated endothelial cells, directly paralleled changes in circulating levels of TNF alpha (r = 0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-1) r = 0.67; P = 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNF alpha levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule-I (sICAM-I) (r = 0.65; P < 0.001) and between sL-selectin and sTNF alpha (r = 0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.
第一，多发性硬化症（MS）患者血液淋巴细胞对用肿瘤坏死因子-α（TNFα）处理的内皮细胞单层的超正常黏附是否是其他炎症性疾病共有的特征；第二，MS患者血液淋巴细胞的黏附特性是否与疾病活动度的变化以及循环TNFα和可溶性黏附分子水平有关。在研究的第一部分，14例MS患者的淋巴细胞比健康对照者的淋巴细胞对TNFα处理的内皮细胞更具黏附性（P<0.01），而12例类风湿性关节炎患者、8例银屑病患者和10例非MS的神经系统疾病患者的淋巴细胞黏附特性正常。在研究的第二阶段，对另外6例MS患者在5至8个月期间每月分离的淋巴细胞的黏附特性进行测量，发现与TNFα处理的内皮细胞结合的变化与TNFα循环水平的变化直接平行（r = 0.77；P<0.001）以及可溶性血管细胞黏附分子-1（sVCAM-1）（r = 0.67；P = 0.001）。通过中枢神经系统（CNS）的T2加权和钆增强磁共振成像测量，有2例患者疾病活动度增加，且与淋巴细胞黏附性增强和血清TNFα水平升高有关。对这6例MS患者的34份血清样本进行进一步分析发现，sL-选择素与可溶性细胞间黏附分子-1（sICAM-1）浓度之间存在直接关系（r = 0.65；P<0.001）以及sL-选择素与sTNFα之间存在直接关系（r = 0.42；P<0.02）。这些发现支持这样一种观点，即MS中的疾病活动与血液淋巴细胞与CNS内炎症部位血管内皮的黏附相互作用增加有关。
