Impairment of JCV-specific T-cell response by corticotherapy: Effect on PML-IRIS management?

This study from Switzerland examined the net effects of corticosteroids (CS) on the virus-specific T-cell responses, especially JC virus, to determine the optimal timing of corticosteroid administration in patients with MS with natalizumab-caused progressive multifocal leucoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS).

The results showed that CS led T cells, either CD4+ or Cd8+, towards a less differentiated phenotype. There was a significant decrease in the proliferation of EBV-, influenza- and JCV-specific T–cell proliferation response upon CS treatment. CS significantly decreased the proliferation of all three virus-specific CD4+ T cells. CS also caused a significant decrease in cytokine production of CD8+ T cells only when these cells were stimulated by JCV, but not EBV or influenza.

Therefore, CS have a significant effect on the virus-specific T-cell response, in particular on JCV, and it is suggested that giving CS before there are signs of immune reconstitution, may be deleterious as such treatment may blunt the JCV-specific T-cell response, leading to the unopposed progression of PML with grim consequences.

When CS are considered, there is conclusive rational to give CS only when the patient shows the first clinical or MRI signs of IRIS. Studies directly addressing patients with MS with natalizumab-caused PML are warranted.

Authors: Antoniol C, Jilek S, Schluep M

Source: Neurology. 2012 Nov 21. [Epub ahead of print]

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