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Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis
S J Khoury1, E J Orav, C R Guttmann
1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard School of Public Health, Boston, MA 02115, USA. khoury@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.
Insights
Serum soluble intercellular adhesion molecule 1 (sICAM-1) and soluble tumor necrosis factor receptors (sTNF-Rs) levels correlate with multiple sclerosis (MS) disease activity. Changes in these markers can precede new MRI lesions, aiding in monitoring MS progression.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Multiple Sclerosis Research
Background:
- Circulating adhesion molecules and soluble receptors may indicate cellular activation and inflammation.
- These molecules can serve as potential biomarkers for inflammatory processes.
Purpose of the Study:
- To investigate changes in serum soluble intercellular adhesion molecule 1 (sICAM-1) and soluble tumor necrosis factor receptors (sTNF-Rs) in MS patients.
- To correlate these changes with clinical disease activity and brain MRI findings.
Main Methods:
- A prospective longitudinal study over 1 year involving 40 MS patients.
- Frequent brain MRI scans (22 per patient) and monthly neurological examinations.
- Assessment of Kurtzke's Expanded Disability Status Scale (EDSS) and ambulation index (AI).
Main Results:
- Relapsing-progressive MS patients showed highest sICAM-1; progressive MS patients showed highest sTNF-Rs.
- sICAM-1 fluctuations correlated with relapses in relapsing and relapsing-progressive MS.
- Increased sICAM-1 preceded new MRI lesions in relapsing-progressive MS; increased sTNF-R p55 preceded lesions in progressive MS.
Conclusions:
- sICAM-1 and sTNF-R levels are linked to MS disease activity.
- Progressive MS patients exhibit distinct immunologic profiles correlated with MRI changes.
- These findings support the use of sICAM-1 and sTNF-Rs for monitoring MS progression and treatment response.