Bridging the Gap: Immunotherapy in Progressive Multifocal Leukoencephalopathy: A New Hope?

Abstract

Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS occurring in immunocompromised individuals in which large demyelinating lesions are induced by polyomavirus JC (JCV). In the absence of effective antiviral treatment, control of the infection relies on restoring anti-JCV immunity. Thus, particularly in long-standing immunocompromising conditions such as organ transplantation, lymphoproliferative disorders, or idiopathic lymphopenia, new strategies to boost anti-JCV immune responses are needed. Here, we report the case of a patient developing PML in the context of kidney transplantation who received recombinant human interleukin 7 to foster immune responses against JCV. We give an overview of the immunologic mechanisms underlying the development of PML and immune restoration within the CNS after JCV infection. Immunotherapeutic strategies developed based on current understanding of the disease hold promise in managing patients with PML.

Figure. Radiologic and Pathologic Features in PML

Representative MRI images showing canonical PML presentation with T2 hyperintense (A) and T1 hypointense (B) lesion of the frontal subcortical white matter and partially involving U fibers. In diffusion-weighted images, the lesion presents a demyelination front (C). Hematoxylin and eosin (HE, D, the position of the inset on the bottom and gray matter/white matter limit are highlighted by dashed lines), Luxol fast blue periodic acid–Schiff (LUPAS, E), and antineurofilament immunostained (NF, F) histologic sections show extensive white matter demyelination with relative preservation of axons. Numerous reactive astrogliosis (GFAP, G) and foamy macrophages (CD68, H) are found within the lesion. JC virus inclusions in nuclei of oligodendrocytes (double arrow in D) and astrocytes (simple arrows in D, G) are highlighted by SV40 immunostaining (I, simple arrows). T-cell infiltration is seen in the perivascular and interstitial spaces (CD3, J), accompanied by perivascular B cells (CD20, K). Scale bars = 5 mm (D–F) and 50 μm (inset on the bottom in D, G–K). PML = progressive multifocal leukoencephalopathy.