Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric refractory epilepsy

被引:13
作者
Saengow, Vitchayaporn Emarach [1 ]
Chiangjong, Wararat [1 ]
Khongkhatithum, Chaiyos [1 ]
Changtong, Channarong [1 ]
Chokchaichamnankit, Daranee [2 ]
Weeraphan, Churat [2 ]
Kaewboonruang, Patcharin [1 ]
Thampratankul, Lunliya [1 ]
Manuyakorn, Wiparat [1 ]
Hongeng, Suradej [1 ]
Srisomsap, Chantragan [2 ]
Svasti, Jisnuson [2 ,3 ]
Chutipongtanate, Somchai [1 ,4 ]
Visudtibhan, Anannit [1 ]
机构
[1] Mahidol Univ, Fac Med, Dept Pediat, Ramathibodi Hosp, Bangkok, Thailand
[2] Chulabhorn Res Inst, Lab Biochem, Bangkok, Thailand
[3] Chulabhorn Grad Inst, Appl Biol Sci Program, Bangkok, Thailand
[4] Mahidol Univ, Fac Med, Dept Clin Epidemiol & Biostat, Ramathibodi Hosp, Bangkok, Thailand
关键词
Biomarker; Intractable seizure; Pediatrics; Plasma proteomics; Refractory epilepsy; CHILDREN; SERUM;
D O I
10.1016/j.braindev.2020.11.001
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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-gamma), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), play roles in pathophysiology in RE patients. Cytokine immunoassay (n = 24, 18 RE vs. 6 controls) exhibited plasma IFN-gamma 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-1 beta was significantly downregulated in patients (1.0 [0.2, 1.9] vs. 4.5 [1.9, 11.0] pg/mL, p = 0.01). TNF-alpha had no difference between groups. The results suggest that haptoglobin may be associated with oxidative brain damage, while IFN-gamma and IL-1 beta may be involved with neuroinflammation. Conclusions: Alterations in plasma haptoglobin, IFN-gamma, and IL-1 beta were associated with RE patients. Future studies using a combination of these candidate biomarkers may help predict the intractability of epilepsy in pediatric populations. (c) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:431 / 439
页数:9
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