Recent progress in the understanding of relevant pathomechanisms of multiple sclerosis (MS) has led to the development of highly specific therapeutic approaches. However, some of these therapeutics have led to severe virologic infections of the brain, e.g. progressive multifocal leukoencephalopathy (PML). The occurrence and key pathomechanisms of PML - an opportunistic JC viral mediated and typically fatal CNS-infection - under monoclonal antiibodies (mAb), e.g. natalizumab, rituximab and efalizumab in otherwise immunocompetent MS (but also psoriasis- and arthritis-) patients remain cryptic. So far, PML was typically associated with severely immunocompromised patients, e.g. HIV or leukemic diseases. In a pilot study, we have established a sensitive immunoassay by quantifying cellular energetics of immune effector cells in response to stimulation as a functional parameter of cellular immunity in over 500 MS patients under various therapies and in 20 recent cases of mAb- and HIV-related PML. To achieve a higher degree of specificity, and concerning the pathogenesis of PML, to identify possible host predisposition, the project as planned in Prof. Fuggers group at the University of Oxford is aiming at immunogenetic (HLA type of PML patients) and immunologic (ability of CD4+/CD8+-cells to response to antigen specific stimulation by the immunodominant JCV epitope(s)) factors leading to the unexpected occurrence of PML in MS patients. By results gained from this study, we await a better understanding of JC viral infection of the CNS which will enable the development of a predictive marker identifying patients at risk for PML.
DFG Programme
Research Fellowships
International Connection
United Kingdom
