Publication: Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy
Issued Date
2021-03-01
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ISSN
18727131
03877604
03877604
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2-s2.0-85097111125
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Mahidol University
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SCOPUS
Bibliographic Citation
Brain and Development. Vol.43, No.3 (2021), 431-439
Suggested Citation
Vitchayaporn Emarach Saengow, Wararat Chiangjong, Chaiyos Khongkhatithum, Channarong Changtong, Daranee Chokchaichamnankit, Churat Weeraphan, Patcharin Kaewboonruang, Lunliya Thampratankul, Wiparat Manuyakorn, Suradej Hongeng, Chantragan Srisomsap, Jisnuson Svasti, Somchai Chutipongtanate, Anannit Visudtibhan Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy. Brain and Development. Vol.43, No.3 (2021), 431-439. doi:10.1016/j.braindev.2020.11.001 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/78427
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Title
Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy
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Abstract
Background: Children with refractory epilepsy (RE) are associated with increased mortality rate, nonfatal injuries, disability, and diminished quality of life. Biomarkers for the early prediction of RE is still an unmet need. Methods: Eighteen children with RE and six age-matched unrelated controls were included in this study. Plasma samples were prefractionated by the optimized thermal treatment before proteomic analysis using 2DE-LC-MS/MS. Bioinformatic analysis was carried out using STRING protein network. Immunoassay of unprocessed plasma was applied to confirm changes of proteins of interest. P-value < 0.05 was considered statistically significant. Results: Proteomic analysis (n = 6 each group) revealed nine differentially expressed proteins, i.e., haptoglobin, S100A9, serpin B1, apolipoprotein A-I, apolipoprotein A-IV, apolipoprotein C-II, alpha-1-acid glycoprotein 1 and 2, and transthyretin. Western immunoblotting confirmed haptoglobin upregulation in the RE group. STRING protein network predicted the inflammatory cytokines, i.e., interferon gamma (IFN-γ), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-γ was upregulated in RE patients as compared to the healthy individuals (median [IQR]; 2.9 [2.9, 4.9] vs. 1.32 [0.8, 1.5] pg/mL, p = 0.0013), and plasma IL-1β was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-α had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-γ and IL-1β may be involved with neuroinflammation. Conclusions: Alterations in plasma haptoglobin, IFN-γ, and IL-1β were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations.