title: Interferon-Stimulated Gene Expression as a Preferred Biomarker for Disease Activity in Aicardi-Goutières Syndrome.
abstract: Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes. Erythrocyte sedimentation rates fluctuated within the normal range for Patient 2, with some elevation, yet, were in the normal range during the second febrile episode when there were accompanying neurological abnormalities. These preliminary data suggest that ISG expression may be a more specific indicator of disease activity in comparison to standard inflammatory markers.
authors.affiliation: 1 Toronto General Research Institute, University Health Network , Toronto, Ontario, Canada .|2 Department of Immunology, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Ben X
authors.initials: BX
authors.lastname: Wang
authors.affiliation: 3 Department of Neurosciences and Mental Health, The Hospital for Sick Children , Toronto, Ontario, Canada .
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Grover
authors.affiliation: 4 Department of Pediatrics, The Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Peter
authors.initials: P
authors.lastname: Kannu
authors.affiliation: 4 Department of Pediatrics, The Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
authors.affiliation: 4 Department of Pediatrics, The Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Laxer
authors.affiliation: 4 Department of Pediatrics, The Hospital for Sick Children, University of Toronto , Toronto, Ontario, Canada .
authors.forename: E Ann
authors.initials: EA
authors.lastname: Yeh
authors.affiliation: 1 Toronto General Research Institute, University Health Network , Toronto, Ontario, Canada .|2 Department of Immunology, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
mesh_terms: D000483:Alleles; D020274:Autoimmune Diseases of the Nervous System / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007223:Infant; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D016914:Ribonuclease H / Q000235:genetics; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D015415:Biomarkers; D007372:Interferons; C091139:ribonuclease HII; D016914:Ribonuclease H
keywords: Aicardi–Goutières syndrome; autoimmunity; interferon-stimulated genes