Immune profile and radiological characteristics of progressive multifocal leukoencephalopathy.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) constitutes a severe disease with increasing incidence, mostly in the context of immunosuppressive therapies. The detailed understanding of immune response in PML appears critical for the treatment strategy. We aimed for a comprehensive immunoprofiling and radiological characterization of MRI-defined PML variants. METHODS: We retrospectively analysed all biopsy-confirmed PML patients (n=15) treated in our department between 01/2004 and 07/2019. Data from magnetic resonance imaging (MRI), histology as well as detailed clinical and outcome data were collected. The MRI-defined PML variants of classical (cPML) and inflammatory (iPML) PML were discriminated based on the intensity of gadolinium enhancement. In these PML variants, we assessed intensity and localization (perivascular vs. parenchymal) of inflammation in MRI and histology as well as the cellular composition by immunohistochemistry. The size of the demyelinating lesions was correlated with immune cell infiltration. RESULTS: Patients with MRI-defined iPML showed a stronger intensity of inflammation with an increased lymphocyte infiltration on histological level. Also, iPML was characterized by a predominantly perivascular inflammation. However, cPML patients also demonstrated certain inflammatory tissue alterations. Infiltration of CD163-positive microglia and macrophage (M/M) subtypes correlated with PML lesion size. CONCLUSIONS: The non-invasive MRI-based discrimination of PML variants allows for an estimation of inflammatory tissue alterations, although exhibiting limitations in MRI-defined cPML. The association of a distinct phagocytic M/M subtype with the extent of demyelination might reflect disease progression.