Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy

Abstract

Natalizumab-induced progressive multifocal leukoencephalopathy appears to be unleashed by complex interactions between viral and immunological host factors leading the latent form of JC virus to become pathogenic. Positive anti-JC virus antibody status, prior use of immunosuppressants, and increasing duration of natalizumab treatment have been proposed as risk factors for progressive multifocal leukoencephalopathy in multiple sclerosis patients, but while they may help to identify the most appropriate patients for natalizumab, their use have some limitations. Therefore, a large body of studies is ongoing to identify alternative, reliable immunological markers capable to improve the safety and efficacy of therapy, and to guide tailored clinical decisions.

Keywords: K-deleting recombination excision circles; Multiple sclerosis; Natalizumab; Progressive multifocal leukoencephalopathy; T-cell receptor excision circles; T-cell receptor repertoire.