Interferon-α and the calcifying microangiopathy in Aicardi–Goutières syndrome

Aicardi-Goutières syndrome is a leukoencephalopathy with calcifications and increased cerebrospinal fluid interferon-α. The relation between interferon-α and brain pathology is poorly understood. We report a patient with mutations in the disease-associated gene SAMHD1. Neuropathology showed an extensive microangiopathy with calcifications consistently associate with blood vessels. In an in vitro model of the microangiopathy, interferon-α enhanced vascular smooth muscle cell-derived calcifications. The noninfarcted white matter harbored apoptotic oligodendrocytes and increased numbers of oligodendrocyte progenitors. These findings better define the white matter pathology and provide evidence that interferon-α plays a direct pathogenetic role in the calcifying angiopathy typical of this disease.