Proteomic analysis reveals plasma haptoglobin, interferon-γ, and interleukin-1β as potential biomarkers of pediatric
Vitchayaporn Emarach Saengow1, Wararat Chiangjong1, Chaiyos Khongkhatithum1
1Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Insights
This study identified potential biomarkers, haptoglobin, interferon gamma (IFN-γ), and interleukin-1 beta (IL-1β), in children with refractory epilepsy (RE). These findings may aid in early prediction and management of pediatric epilepsy.
Area of Science:
- Proteomics and biomarker discovery in pediatric neurology.
- Investigating molecular mechanisms of refractory epilepsy.
Background:
- Refractory epilepsy (RE) in children leads to severe health issues and reduced quality of life.
- Early prediction biomarkers for pediatric RE are currently lacking.
Purpose of the Study:
- To identify novel plasma biomarkers for early prediction of refractory epilepsy in children.
- To explore the role of specific proteins and cytokines in RE pathophysiology.
Main Methods:
- Proteomic analysis (2DE-LC-MS/MS) of plasma samples from children with RE and controls.
- Bioinformatic analysis using STRING protein network to identify key pathways.
- Immunoassay validation of differentially expressed proteins and cytokines.
Main Results:
- Nine differentially expressed proteins were identified, including haptoglobin, which was upregulated in RE patients.
- Interferon gamma (IFN-γ) was upregulated, and interleukin-1 beta (IL-1β) was downregulated in RE patients.
- Haptoglobin may link to oxidative brain damage, while IFN-γ and IL-1β suggest involvement in neuroinflammation.
Conclusions:
- Plasma haptoglobin, IFN-γ, and IL-1β alterations are associated with refractory epilepsy in children.
- These biomarkers show promise for predicting epilepsy intractability in pediatric populations.
- Further research combining these biomarkers could improve early diagnosis and treatment strategies.
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.
