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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.
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.
GLOSSARY
- AGS=
- Aicardi-Goutières syndrome;
- CCL2=
- chemokine (C-C motif) ligand 2;
- CXCL10=
- C-X-C motif chemokine 10;
- Flt-3L=
- FMS-related tyrosine kinase 3 ligand;
- G-CSF=
- granulocyte colony stimulating factor;
- IFN=
- interferon;
- IL=
- interleukin;
- MCP-1=
- monocyte chemotactic protein–1;
- sIL-2rα=
- soluble interleukin 2 receptor α;
- TNF=
- tumor necrosis factor
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received September 25, 2009.
- Accepted December 11, 2012.
- © 2013 American Academy of Neurology
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