Elovaara I, Ukkonen M, Leppäkynnäs M, Lehtimäki T, Luomala M, Peltola J, Dastidar P
Department of Neurology, Tampere University Hospital, Finland.
Arch Neurol. 2000 Apr;57(4):546-51. doi: 10.1001/archneur.57.4.546.
To determine levels of adhesion molecules in blood and cerebrospinal fluid (CSF) samples from patients with different subtypes and activities of multiple sclerosis (MS) and to assess the effect of intravenous methylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules.
The expressions of very late activation antigen 4 (VLA-4), lymphocyte function associated antigen 1 (LFA-1), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were determined immunocytochemically, and levels of soluble VCAM-1, ICAM-1, and E-selectin, by means of enzyme immunoassay technique. The volumes of T2- and T1-weighted MS plaques and brain atrophy were determined by means of the semiautomatic magnetic resonance imaging (MRI) segmentation technique.
A university hospital in Finland.
One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), secondary progressive (SPMS [n = 20]), and primary progressive (PPMS [n = 25]).
In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in controls (RRMS, P = .002 and P<.001, respectively; SPMS, P = .03 and P =.001, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up-regulated than in SPMS (P = .03 and P = .01, respectively). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-1-expressing lymphocytes were 3- to 4-fold higher than in controls (P = .04 and P = .008, respectively). The levels of serum soluble VCAM-1 were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of patients with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P<.001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; P = .03).
Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.
测定不同亚型和活动期的多发性硬化症（MS）患者血液和脑脊液（CSF）样本中黏附分子的水平，并评估静脉注射琥珀酸钠甲泼尼龙治疗对可溶性黏附分子水平的影响。
采用免疫细胞化学方法测定极晚期活化抗原4（VLA-4）、淋巴细胞功能相关抗原1（LFA-1）、血管细胞黏附分子1（VCAM-1）和细胞间黏附分子1（ICAM-1）的表达，并通过酶免疫测定技术检测可溶性VCAM-1、ICAM-1和E-选择素的水平。采用半自动磁共振成像（MRI）分割技术测定T2加权和T1加权MS斑块的体积及脑萎缩情况。
芬兰的一家大学医院。
100名受试者（71例MS患者和29名健康对照者）。MS的亚型为复发缓解型（RRMS [n = 26]）、继发进展型（SPMS [n = 20]）和原发进展型（PPMS [n = 25]）。
RRMS和SPMS患者血液中免疫细胞上VLA-4和LFA-1的表达比对照组至少高1.5至3倍（RRMS分别为P = 0.002和P<0.001；SPMS分别为P = 0.03和P = 0.001）。在RRMS中，血液中LFA-1和ICAM-1的表达上调程度高于SPMS（分别为P = 0.03和P = 0.01）。RRMS和SPMS患者脑脊液淋巴细胞上黏附分子的表达幅度相似，但表达VLA-4和LFA-1的脑脊液淋巴细胞比例比对照组高3至4倍（分别为P = 0.04和P = 0.008）。SPMS患者血清可溶性VCAM-1水平高于RRMS（P = 0.005）或PPMS（P = 0.04）。对RRMS急性加重期患者进行静脉注射甲泼尼龙治疗后，血清可溶性VCAM-1和E-选择素水平显著降低（P<0.001）。在SPMS中，T2加权斑块体积与血清可溶性ICAM-1水平相关（r = 0.64；P = 0.03）。
血液和脑脊液中黏附分子上调表明在MS整个临床病程中CNS存在持续的炎症潜能。干扰细胞黏附的治疗方法对抑制MS可能至关重要。
