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Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis

From the Center for Neurologic Diseases (Drs. Khoury and Weiner) and the Radiology Department (Drs. Guttmann, Kikinis, and Jolesz), Brigham and Women’s Hospital; and the Department of Biostatistics (Dr. Orav), Harvard School of Public Health, Boston, MA.

Address correspondence and reprint requests to Dr S.J. Khoury, Center for Neurologic Diseases, 77 Avenue Louis Pasteur, Boston, MA 02115; e-mail: khoury{at}cnd.bwh.harvard.edu

OBJECTIVE: To study the change in serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble tumor necrosis factor receptors (sTNF-Rs) in MS patients in relation to clinical disease activity and changes on brain MRI.

BACKGROUND: Circulating forms of adhesion molecules or soluble receptors may be released from cells as a consequence of activation and may be useful markers for inflammation.

METHODS: During a prospective longitudinal study over 1 year, 40 patients with MS underwent frequent imaging of the brain (22 MR images per patient) at the time of blood sampling as well as monthly neurologic examinations, and scoring on Kurtzke’s Expanded Disability Status Scale (EDSS) and ambulation index (AI).

RESULTS: Patients with relapsing–progressive disease had the highest levels of sICAM-1 whereas patients with progressive disease had the highest levels of sTNF-Rs. Fluctuations in sICAM-1 correlated with the occurrence of attacks in patients with relapsing and relapsing–progressive disease. In patients with relapsing–progressive MS, an increase in sICAM-1 level preceded the appearance of new gadolinium (Gd) enhancing lesions on MRI. In patients with progressive disease, an increase in sTNF-R p55 level preceded the appearance of new Gd enhancing lesions on MRI, whereas a decrease in sICAM-1 levels correlated with the appearance of new Gd enhancing lesions.

CONCLUSIONS: These results demonstrate a linkage between sICAM-1 and sTNF-R levels and disease activity in MS. Furthermore, patients with progressive disease appear to have a different immunologic stage of disease in which immune changes are tightly linked with changes on MRI. The demonstration of a correlation in individual patients between immunologic events and changes in disease activity has implications for monitoring patients undergoing treatment and for monitoring disease progression.

Key words: Soluble intercellular adhesion molecule 1—Soluble tumor necrosis factor receptors—MS—Brain MRI.

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