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Relation to Subtypes of Disease and Methylprednisolone Therapy

Irina Elovaara, MD, PhD; Maritta Ukkonen, MD; Minna Leppäkynnäs, MD; Terho Lehtimäki, MD, PhD; Mari Luomala, MSc; Jukka Peltola, MD; Prasun Dastidar, MD

Arch Neurol. 2000;57:546-551.

Objectives  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.

Design  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.

Setting  A university hospital in Finland.

Patients  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]).

Results  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).

Conclusions  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.

From the Neuroimmunology Unit, Department of Neurology (Drs Elovaara, Ukkonen, Leppäkynnäs, and Peltola and Ms Luomala), and the Department of Diagnostic Radiology (Dr Dastidar), Tampere University Hospital, and the Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, Medical School of Tampere University (Dr Lehtimäki and Ms Luomala), Tampere, Finland.

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