Temporal variations of adhesion molecules and matrix metalloproteinases in the course of MS

Thirty patients with clinically isolated syndromes (CIS) were evaluated at the onset of neurological symptoms and when they developed clinically definite MS (CDMS). Surface expression of LFA-1, VLA-4 and intercellular adhesion molecule-1 (ICAM-1) on PBMC and CSF cells was evaluated using flow cytometry. Serum and CSF concentrations of soluble vascular cell adhesion molecules-1 (VCAM-1), ICAM-1 and E-Selectin, as well as MMP-9 and MMP-2 serum concentrations were assayed using ELISA. Surface expression of LFA-1 and VLA-4 molecules on peripheral blood and CSF T cells and monocytes from CIS and CDMS was significantly increased compared with control subjects. Moreover, LFA-1 and VLA-4 expression was significantly higher in patients who developed CDMS compared with those with CIS. Similar changes were observed in the serum levels of MMP-9. Furthermore, patients with CIS and CDMS had significantly higher levels of CSF sVCAM and s-E-Selectin than control subjects. These data suggest that VLA-4, LFA-1 and MMP-9 play a leading role in the evolution of inflammatory demyelinating lesions in patients with CIS who develop CDMS.