T cell deficiencies as a common risk factor for drug associated progressive multifocal leukoencephalopathy

Immunobiology
Dejan PavlovicProgressive Multifocal Leukoencephalopathy Consortium

Abstract

Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system caused by neuropathogenic prototypes of ubiquitous community-acquired JC virus (JCV). The disease became of particular concern following its association with certain therapies that modulate immune system function without heavy immunosuppression. Due to lack of prophylactic/treatment options and poor outcomes, which often include severe disability or death, PML is a considerable concern for development of new drugs that interfere with immune system functions. In this review of clinical and research findings, we discuss the evidence that deficiencies in CD4+ T helper cells, cytotoxic CD8+ T cells, and interferon gamma are of crucial importance for development of PML under a variety of circumstances, including those associated with use of various drugs, regardless of differences in their mechanisms of action. These deficiencies apparently enable transformation of the harmless JCV archetype into neuropathogenic prototypes, but the site(s), and the mechanisms, of this transformation are yet to be elucidated. Here we discuss the evidence for brain as one of the sites of this transformation, and propose a model of PML pathogenesis that emphasiz...Continue Reading

Citations

Sep 5, 2020·Viruses·Abigail L Atkinson, Walter J Atwood
Sep 1, 2020·The Journal of Clinical Investigation·Jose S CamposRoshini S Abraham
Nov 22, 2020·Nature Reviews. Neurology·Irene CorteseAvindra Nath

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