Although most of the
progressive multifocal leukoencephalopathy cases in
sarcoidosis patients are explained by the treatment with immunosuppressive drugs, it is also reported in treatment-naive
sarcoidosis patients, which implies a general predisposition of
sarcoidosis patients for
progressive multifocal leukoencephalopathy. Indeed, it was shown that active
sarcoidosis patients have increased regulatory T cell frequencies which could lead to a subsequent systemic immunosuppression. However, if
sarcoidosis with systemic changes of T cell subsets frequencies constitute a risk factor for the development of
progressive multifocal leukoencephalopathy, which could then be counteracted by
sarcoidosis treatment, is not known. In this cohort study, we included, characterized and followed-up six patients with bioptically confirmed definite
progressive multifocal leukoencephalopathy and definite or probable
sarcoidosis presenting between April 2013 and January 2019, four of them had no immunosuppressive therapy at the time of developing first
progressive multifocal leukoencephalopathy symptoms. Analysis of immune cell subsets in these patients revealed significant imbalances of CD4+ T cell and regulatory T cell frequencies. Due to the progression of
progressive multifocal leukoencephalopathy in four patients, we decided to treat
sarcoidosis anticipating normalization of immune cell subset frequencies and thereby improving
progressive multifocal leukoencephalopathy. Notably, by treatment with
infliximab, an antibody directed against tumour
necrosis factor-α, three patients continuously improved clinically, JC virus was no longer detectable in the cerebrospinal fluid and regulatory T cell frequencies decreased. One patient was initially misdiagnosed as
neurosarcoidosis and died 9 weeks
after treatment initiation due to
aspiration pneumonia. Our study provides insight that
sarcoidosis can lead to changes in T cell subset frequencies, which predisposes to
progressive multifocal leukoencephalopathy. Although immunosuppressive drugs should be avoided in
progressive multifocal leukoencephalopathy, paradoxically in patients with
sarcoidosis treatment with the immunosuppressive
infliximab might restore normal T cell distribution and thereby halt
progressive multifocal leukoencephalopathy progression.