 |
|
Adhesion Molecules in Multiple Sclerosis
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.
RELATED ARTICLE
Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2000;57(4):613-614.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis
Ukkonen et al.
Mult Scler 2007;13:701-707.
ABSTRACT
Serum immunologic markers in multiple sclerosis patients on continuous combined therapy with beta-interferon 1a, prednisone and azathioprine
Hashemi et al.
Mult Scler 2006;12:652-658.
ABSTRACT
The mechanism of action of methylprednisolone in the treatment of multiple sclerosis
Sloka and Stefanelli
Mult Scler 2005;11:425-432.
ABSTRACT
An open-label safety and drug interaction study of natalizumab (AntegrenTM) in combination with interferon-beta (Avonex(R)) in patients with multiple sclerosis
Vollmer et al.
Mult Scler 2004;10:511-520.
ABSTRACT
Randomized multicenter trial of natalizumab in acute MS relapses: Clinical and MRI effects
O'Connor et al.
Neurology 2004;62:2038-2043.
ABSTRACT
| FULL TEXT
Methylprednisolone Acts on Peripheral Blood Mononuclear Cells and Endothelium in Inhibiting Migration Phenomena in Patients With Multiple Sclerosis
Gelati et al.
Arch Neurol 2002;59:774-780.
ABSTRACT
| FULL TEXT
|
