The risk of relapses in multiple sclerosis during systemic infections.
OBJECTIVE
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-gamma, TNFalpha, 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-gamma, TNFalpha, 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.
Correale
Jorge
J
Department of Neurology, Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina. jcorreale@fleni.org.ar
Fiol
Marcela
M
Gilmore
Wendy
W
D000328:Adult; D001424:Bacterial Infections / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D002140:California / Q000453:epidemiology; D015897:Comorbidity; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines