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 i ntercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) are useful as surrogate markers of disease activi ty in multiple sclerosis (MS). Background: Increased levels of sICAM-1 and sVCAM-1 have been described in cross-sectional, but not longitudi nal, studies of patients with MS. Although they appear to correlate wi th clinical and MRI markers of disease activity, their role as potenti al surrogate markers remains undefined. Methods: Serial serum levels o f sICAM-1 and sVCAM-1 were measured in patients with MS undergoing mon thly gadolinium-enhanced MRI studies of the brain (462 gadolinium-enha nced MRI in 57 patients) and in 12 normal control subjects. Ten patien ts had primary progressive (PP), 22 relapsing remitting (RR), and 25 s econdary progressive (SP) disease. Results: Levels of sICAM-1 and sVCA M-1 were increased intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were elevated in patients with MS compared w ith normal controls (normal controls median [interquartile range] = 17 6[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 l evels (0.4[0-2.7], p = 0.03), and patients with MRI studies with no ga dolinium-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 R R or SP disease that progressed clinically during the study had a grea ter 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 d id 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 fi nding was not significant. No correlation could be found between level s of sVCAM-1 and gadolinium enhancement on MRI. Conclusions: Patients with MS have elevated levels of sICAM-1, which correlate with gadolini um enhancement on MRI and possibly short-term disease progression. Sol uble ICAM-1, and not sVCAM-1, may therefore be suitable as a long-term surrogate marker of disease activity in MS.