The risk of relapses in multiple sclerosis during systemic infections
Correale J, Fiol M, Gilmore W;
Commented by , 27 Sep 2006
Background
It has been described that systemic infections (SI) increase the risk and severity of exacerbations in multiple sclerosis (MS). This relationship has been related to viral infections of the upper respiratory or gastrointestinal tract and not to bacterial infections of e.g. the urinary tract. The current study re-evaluate the risk of MS relapses during systemic infections and furthermore apply an extensive battery of immunological tests.
Aim
To assess the risk of MS relapses, MRI activity and T cell responses during systemic infections.
Methods
The study prospectively included 60 patients with relapsing remitting MS, who were followed for an average of 20.45 ±3.5 months pr. patient. Information regarding infections and relapses were collected, and in a subgroup of 20 patients, MRI examinations were performed at onset of SI relapse and after 2 and 12 weeks. A number of immunological tests were carried out including IL-4, IL-10, IL-12, IFN-γ, TNF-α, VLA-4, LFA-1, MMP-9 and MMP-2, after infectious antigen (Ag) stimulation.
Results
The authors recorded 127 infections in 53 patients (88%) and 52% of these were infections of the upper respiratory tract, 42.5% urinary tract, and 5.5% gastrointestinal tract. The etiology was documented in 57% of all infections.
Increased risk of relapse and MRI activity (Gd+ lesions) was observed during SI (annual relapse rate 3.05 during risk and 0.93 outside risk, OR 3.2; CI 2.25-4.69).
Relapses characterized as major, long and sustained were also increased during SI.
Measurements of IFN-γ, TNF-α, and IL-12 secreting cells, serum concentrations of MMP-9 and expression of VLA-4 and LFA-1, were higher after viral or bacterial stimulation during exacerbations associated to SI.
The infectious antigen had little effect on peripheral blood myelin specific T cell activity, but the additional presence of cognate myelin Ag induced significant autoreactive T cell proliferation.
Dr Blinkenberg's comments
The study confirms that MS relapses may be triggered by microbial infections. The risk of relapse is increased approximately three times compared with periods of no infection risk, which is in line with previous studies.
Furthermore, the study show that exacerbations associated to infections, leads to more severe and sustained neurological deterioration.
The authors find no difference between bacterial and viral infections associated with relapse, which contradicts findings of previous studies, and there was no obvious bias in the data that could explain this discrepancy. The possible clinical implication in this regard, is more extensive antibiotic prophylaxis in MS patients predisposed to e.g. urinary tract infections, and it also emphasizes the need for thorough counseling in order to prevent and treat common SI.
Another interesting result is the effect of cognate antigen activation that, in combination with infectious antigens, increases the proliferation of autoreactive T cells considerably. It seems like microbial antigens and proinflammatory cytokine secretion alone can not drive expansion or activation of MBP- and MOG-specific T cells, indicating that autoimmunity in MS is initiated by cross-reactivity between antigens of an infectious agent and the host. These findings will need further investigation.
Finally, it should be mentioned that the non-blinded explorative study design weakens the validity of the study, and it would be interesting to see controlled data from a study in this field.