Brain, Vol. 122, No. 12, 2297-2307,
December 1999
© 1999 Oxford University Press
Review article |
Immunological profile of patients with primary progressive multiple sclerosis
Expression of adhesion molecules
Unitat de Neuroimmunologia Clínica, Servei de Neurologia, Hospital General Universitari Vall d'Hebron, Barcelona, Spain
Correspondence to:
Isabel Durán, Unitat de Neuroimmunologia Clínica, Escola d'Infermeria 5a planta, Hospital General Universitari Vall d'Hebron, Psg. Vall d'Hebron 119129, 08035, Barcelona, Spain E-mail: iduran{at}hg.vhebron.es
Adhesion molecules are important in the trafficking of peripheral leucocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis, which is an inflammatory and demyelinating disease. The latest MRI evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of elucidating whether different pathogenic mechanisms are involved in primary progressive multiple sclerosis, we compared membrane expression of the adhesion molecules ICAM-1 (CD54), LFA-1
(CD11a), VLA-4 [
4/ß1 integrin (CD49d/CD29)], L-selectin (CD62L) and ICAM-3 (CD50) in peripheral blood and the serum-soluble forms ICAM-1, L-selectin, VCAM-1 and ICAM-3 in 89 patients (39 with the primary progressive form, 25 with the secondary progressive form and 25 with the relapsingremitting form) and 38 healthy controls. We found a significant decrease in leucocyte surface expression of most of the adhesion molecules tested and an increase in soluble ICAM-1 and L-selectin levels in secondary progressive and relapsingremitting multiple sclerosis compared with primary progressive multiple sclerosis, which gave results similar to those in controls. These results, which are supported by MRI evidence, show that trafficking of autoreactive leucocytes through the bloodbrain barrier is crucial to the pathogenesis of secondary progressive and relapsingremitting forms of multiple sclerosis, whereas other mechanisms leading to progressive axonal damage would account for primary progressive forms of the disease.
multiple sclerosis; primary progressive; adhesion molecules; bloodbrain barrier
CPMS = `chronic progressive' multiple sclerosis; ELISA = enzyme-linked immunosorbent assay; PBL = peripheral blood lymphocytes; PPMS = primary progressive multiple sclerosis; RRMS = relapsingremitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis. For abbreviations for monoclonal antibodies, see section headed Reagents.
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