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The risk of relapses in multiple sclerosis during systemic infections

From the Department of Neurology (J.C., M.F.), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina; and Departments of Neurology and Cell and Neurobiology (W.G.), Keck School of Medicine, University of Southern California, Los Angeles.

Address correspondence and reprint requests to Dr. Jorge Correale, Raúl Carrea Institute for Neurological Research, FLENI., Montañeses 2325, (1428) Buenos Aires, Argentina; e-mail: jcorreale{at}fleni.org.ar.

Objectives: To assess the risk of multiple sclerosis (MS) relapses, MRI activity, and T cell responses during systemic infections (SI) in patients with MS.

Methods: The authors prospectively studied 60 patients with MS. Twenty patients were evaluated with sequential MRI on initial visit, and 2 and 12 weeks later. Blood samples were collected at first infection symptom and 2, 5, 12, and 24 weeks later, and production of IL-4, IL-10, IL-12, IFN-, TNF, VLA-4, LFA-1, MMP-9, and MMP-2 were measured after infectious antigens (Ag) stimulation.

Results: Increased risk of relapse and MRI activity were observed during SI. Numbers of IFN-, TNF, and IL-12 secreting cells, serum concentrations of MMP-9, and expression of VLA-4 and LFA-1 after PBMC viral or bacterial Ag stimulation were higher in samples collected during exacerbations associated to SI. Transwell analysis demonstrated that soluble factors produced during viral stimulation have little effect on myelin specific T cells activity. In contrast, PBMC viral stimulation in the presence of cognate myelin Ag induces maximal effector responses at 20 to 30 times lower than the Ag alone.

Conclusions: There was a significant association between systemic infections and risk of MS relapse, increased MRI activity, and T cells activation. Furthermore, infectious agents increased myelin specific T-cells sensitivity to cognate Ag.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the August 22 issue to find the title link for this article.

This article was previously published in electronic format as an Expedited E-Pub on July 26, 2006, at www.neurology.org.

Disclosure: The authors report no conflicts of interest.

Received December 23, 2005.

Accepted in final form March 27, 2006.

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