title: Elevation of proinflammatory cytokines in patients with Aicardi-Goutières syndrome.
abstract: OBJECTIVE
  This study explores a large panel of cytokines in plasma and CSF of patients with Aicardi-Goutières syndrome (AGS) at different ages, in order to establish signatures of cytokines most predictive of AGS.
  
  
  METHODS
  Plasma from 22 subjects with known mutations were assayed for cytokines using the Milliplex MAP Immunobead system, and compared to results from 8 age-matched normal controls. CSF of 11 additional patients with mutation-proven AGS was tested in an identical manner and compared to results from age-matched controls. Samples were banked and analysis was carried out retrospectively.
  
  
  RESULTS
  Significant elevations were seen in FMS-related tyrosine kinase 3 ligand, IP-10, interleukin (IL)-12p40, IL-15, tumor necrosis factor α, and soluble IL 2 receptor α in both AGS patient plasma and CSF relative to controls. Additionally, this cytokine signature was able to correctly cluster 9 of 11 AGS cases based on CSF values. While most cytokines decreased exponentially with age, a subgroup including IP-10 demonstrated persistent elevation beyond early childhood.
  
  
  CONCLUSIONS
  Patients with AGS exhibit plasma and CSF elevations of proinflammatory cytokines. Selected cytokines remain persistently elevated beyond the initial disease phase. This panel of proinflammatory cytokines may be considered for use as diagnostic and therapeutic markers of disease, and may permit improved understanding of disease pathogenesis.
authors: Center for Genetic Medicine Research, Department of Neurology, Children's National Medical Center, Washington, DC, USA.
authors: Asako
authors: A
authors: Takanohashi
authors: Morgan
authors: M
authors: Prust
authors: Jichuan
authors: J
authors: Wang
authors: Heather
authors: H
authors: Gordish-Dressman
authors: Miriam
authors: M
authors: Bloom
authors: Gillian I
authors: GI
authors: Rice
authors: Johanna L
authors: JL
authors: Schmidt
authors: Yanick J
authors: YJ
authors: Crow
authors: Pierre
authors: P
authors: Lebon
authors: Taco W
authors: TW
authors: Kuijpers
authors: Kanneboyina
authors: K
authors: Nagaraju
authors: Adeline
authors: A
authors: Vanderver
mesh_terms: D000293:Adolescent; D020274:Autoimmune Diseases of the Nervous System / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D009421:Nervous System Malformations / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators