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Immunological profile of patients with primary progressive multiple sclerosis. Expression of adhesion molecules
I Durán1, E M Martínez-Cáceres, J Río
1Unitat de Neuroimmunologia Clínica, Servei de Neurologia, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. iduran@hg.vhebron.es
Abstract:
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-1alpha (CD11a), VLA-4 [alpha(4)/beta(1) 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 relapsing-remitting 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 relapsing-remitting 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 blood-brain barrier is crucial to the pathogenesis of secondary progressive and relapsing-remitting forms of multiple sclerosis, whereas other mechanisms leading to progressive axonal damage would account for primary progressive forms of the disease.
Insights
In multiple sclerosis, adhesion molecule changes differ between progressive and relapsing forms. Primary progressive MS shows fewer changes, suggesting distinct disease mechanisms compared to relapsing forms.
Area of Science:
- Neuroimmunology
- Cellular and Molecular Medicine
Background:
- Multiple sclerosis (MS) pathogenesis involves leukocyte trafficking into the central nervous system.
- Distinct clinical and MRI findings suggest different mechanisms in primary progressive MS (PPMS) versus relapsing forms.
Purpose of the Study:
- To investigate differences in adhesion molecule expression between PPMS, secondary progressive MS (SPMS), and relapsing-remitting MS (RRMS).
- To elucidate distinct pathogenic mechanisms in PPMS.
Main Methods:
- Compared membrane and soluble adhesion molecule levels (ICAM-1, LFA-1alpha, VLA-4, L-selectin, ICAM-3, VCAM-1) in 89 MS patients and 38 controls.
- Utilized peripheral blood analysis and serum assays.
- Correlated findings with MRI evidence.
Main Results:
- PPMS patients showed adhesion molecule levels similar to healthy controls.
- SPMS and RRMS patients exhibited decreased leukocyte surface adhesion molecules and increased soluble ICAM-1 and L-selectin.
- These differences suggest distinct trafficking roles in MS pathogenesis.
Conclusions:
- Leukocyte trafficking via the blood-brain barrier is critical in SPMS and RRMS pathogenesis.
- PPMS likely involves alternative mechanisms driving progressive axonal damage.
- Adhesion molecule profiles differentiate MS subtypes, aiding understanding of disease mechanisms.