title: Cerebral Spinal Fluid levels of Cytokines are elevated in Patients with Metachromatic Leukodystrophy.
abstract: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease resulting from a deficiency of arylsulfatase A causing an accumulation of cerebroside sulfate, a lipid normally abundant in myelin. Sulfatide accumulation is associated with progressive demyelination and a clinical presentation in severe disease forms that is dominated by motor manifestations. Cerebral inflammation may contribute to the pathophysiology of MLD. To date, cytokine levels in the cerebral spinal fluid of MLD patients have not previously been reported. The objective of this study was to evaluate the concentration of inflammatory cytokines in the CSF of patients with MLD and to compare these levels to unaffected controls. Of 22 cytokines evaluated, we documented significant elevations of MCP-1, IL-1Ra, IL-8, MIP-1b and VEGF in the MLD patients compared to unaffected controls. The elevated cytokines identified in this study may play a significant role in the pathophysiology of MLD. Better understanding of the inflammatory and neurodegenerative process of MLD may lead to improved targeted therapies.
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Thibert
authors.affiliation: Division of Pediatric Neurology, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Weston P
authors.initials: WP
authors.lastname: Miller
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, 55455, US.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000134:cerebrospinal fluid*; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid*; D007966:Leukodystrophy, Metachromatic / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators