Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging.
OBJECTIVE
To assess whether serial serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activity in multiple sclerosis (MS).


BACKGROUND
Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudinal, studies of patients with MS. Although they appear to correlate with clinical and MRI markers of disease activity, their role as potential surrogate markers remains undefined.


METHODS
Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary progressive (SP) disease.


RESULTS
Levels of sICAM-1 and sVCAM-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared with normal controls (normal controls median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium-enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium-enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497 ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed clinically during the study had a greater number of gadolinium-enhancing lesions per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have higher sVCAM-1 levels than did normal controls, this finding was not significant. No correlation could be found between levels of sVCAM-1 and gadolinium enhancement on MRI.


CONCLUSIONS
Patients with MS have elevated levels of sICAM-1, which correlate with gadolinium enhancement on MRI and possibly short-term disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.
Giovannoni
G
G
Institute of Neurology, Department of Neuroimmunology, London, UK.
Lai
M
M
Thorpe
J
J
Kidd
D
D
Chamoun
V
V
Thompson
A J
AJ
Miller
D H
DH
Feldmann
M
M
Thompson
E J
EJ
D000328:Adult; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D005682:Gadolinium; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis; D012737:Sex Factors; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D015415:Biomarkers; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005682:Gadolinium