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.
Department of Pediatrics/Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
Melanie D
MD
Klok
Department of Pediatrics/Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
Hannah S
HS
Bakels
Department of Pediatrics/Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
Nienke L
NL
Postma
Department of Clinical Genetics, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
Rosalina M L
RM
van Spaendonk
Department of Pediatrics/Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands ; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, The Netherlands.
Marjo S
MS
van der Knaap
Department of Pediatrics/Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands ; Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
Marianna
M
Bugiani