TY - JOUR
T1 - Elevation of proinflammatory cytokines in patients with Aicardi-Goutières syndrome.
AU - Takanohashi, Asako
AU - Prust, Morgan
AU - Wang, Jichuan
AU - Gordish-Dressman, Heather
AU - Bloom, Miriam
AU - Rice, Gillian I
AU - Schmidt, Johanna L
AU - Crow, Yanick J
AU - Lebon, Pierre
AU - Kuijpers, Taco W
AU - Nagaraju, Kanneboyina
AU - Vanderver, Adeline
N1 - 1U54HD053177-01A1, NICHD NIH HHS, United States2R24HD050846-06, NICHD NIH HHS, United StatesK26 OD011171, NIH HHS, United StatesK26OD011171, NIH HHS, United StatesR01-AR050478, NIAMS NIH HHS, United States
PY - 2013/3/12
Y1 - 2013/3/12
N2 - 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. CONCLUSION: 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.
AB - 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. CONCLUSION: 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.
U2 - 10.1212/WNL.0b013e3182872694
DO - 10.1212/WNL.0b013e3182872694
M3 - Article
C2 - 23408864
SN - 1526-632X
VL - 80
SP - 997
EP - 1002
JO - Neurology
JF - Neurology
IS - 11
ER -