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Diagnostic utility of circulating interleukin-1 beta and microRNA-146a in differentiating febrile seizures from other pediatric conditions
Saeed Mohammadi, Mwssa Abbood Hameed Ati, Fakhri Sadat Seyedhosseini, Mojtaba Zare Ebrahimabad, Mohsen Saeidi, Seyed Ahmad Hosseini, Mahmoud Darweesh, Ahmed Al-Harrasi, Yaghoub Yazdani
Saeed Mohammadi, Mahmoud Darweesh, Ahmed Al-Harrasi, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, Ad Dakhiliyah, Oman
Saeed Mohammadi, Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Mwssa Abbood Hameed Ati, Department of Immunology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Fakhri Sadat Seyedhosseini, Department of Internal Medicine, School of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Mojtaba Zare Ebrahimabad, Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Mohsen Saeidi, Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Seyed Ahmad Hosseini, Department of Pediatrics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Yaghoub Yazdani, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Golestān, Iran
Co-corresponding authors: Ahmed Al-Harrasi and Yaghoub Yazdani.
Author contributions: Mohammadi S and Yazdani Y contributed to the study conception; Mohammadi S, Zare Ebrahimabad M, and Darweesh M contributed to the methodology (design); Seyedhosseini FS contributed to data collection; Mohammadi S was responsible for data curation (preparation); Ati MAH performed the formal analysis; Zare Ebrahimabad M conducted the data analysis and software implementation; Mohammadi S was responsible for original draft preparation; Seyedhosseini FS, Darweesh M, and Yazdani Y contributed to the review and editing of the manuscript; Saeidi M, Al-Harrasi A, and Yazdani Y provided supervision. Saeidi M and Al-Harrasi A handled project administration; Mohammadi S and Saeidi M provided resources; Yazdani Y was responsible for funding acquisition; Ati MAH and Hosseini SAH performed validation; Hosseini SAH provided clinical expertise and assisted with patient recruitment; Al-Harrasi A and Yazdani Y contributed equally to this manuscript and are co-corresponding authors. All authors have read and approved the final manuscript.
Supported by the Department of Research and Technology, Golestan University of Medical Sciences, Iran, No. 113610; and the Oman Ministry of Higher Education, Research, and Innovation, No. BFP/RGP/HSS/24/015.
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Golestan University of Medical Sciences (No. IR.GOUMS.REC.1402.114).
Informed consent statement: Written informed consent was obtained from the parents or legal guardians of all participating children prior to their inclusion in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The data presented in this study are available on request.
Corresponding author: Yaghoub Yazdani, PhD, Laboratory Sciences Research Center, Golestan University of Medical Sciences, Hirkania BLVD, Gorgan 4934174515, Golestān, Iran.
yazdani@goums.ac.ir
Received: July 16, 2025
Revised: August 6, 2025
Accepted: January 5, 2026
Published online: March 20, 2026
Processing time: 241 Days and 22.5 Hours
BACKGROUND
Febrile seizures (FS) are common pediatric neurological disorders typically triggered by fever, affecting children aged 6 months to 5 years. Although usually benign, early and accurate diagnosis is crucial for effective management.
AIM
To investigate the diagnostic potential of interleukin-1 beta (IL-1β) and microRNA-146a (miR-146a) in distinguishing FS from healthy subjects (HS), fever-only (FO), and seizure-only (SO) cases.
METHODS
Pediatric patients were grouped into FS (n = 68), HS (n = 52), FO (n = 52), and SO (n = 32). Blood samples were collected within 30 minutes of seizure onset or fever presentation. Plasma samples were analyzed for IL-1β (enzyme-linked immunosorbent assay) and miR-146a (real-time polymerase chain reaction). Group comparisons were conducted using analysis of variance or the non-parametric alternative (Kruskal-Wallis test), while diagnostic performance was evaluated through receiver operating characteristic curve analysis.
RESULTS
IL-1β levels showed the highest level in FS, followed by FO and SO, with HS showing the lowest levels. IL-1β distinguished FS from HS with an area under the curve (AUC) of 0.9983 (sensitivity: 100%, specificity: 96.15%). miR-146a was lowest in FS and highest in HS, achieving an AUC of 1.000 (sensitivity: 100%, specificity: 98.08%). IL-1β and miR-146a also effectively differentiated FS from FO and SO, with respective AUCs of 0.8862 and 0.8173 for FS vs FO.
CONCLUSION
IL-1β and miR-146a could be promising diagnostic biomarkers for FS, distinguishing FS from HS, FO, and SO with high sensitivity and specificity. These markers possess the potential to enhance early FS diagnosis.
Core Tip: This study assessed the diagnostic potential of interleukin-1 beta and microRNA-146a in distinguishing febrile seizures (FS) from healthy subjects, fever-only, and seizure-only cases. Interleukin-1 beta levels were significantly highest in the FS group, while microRNA-146a levels were lowest in FS and highest in healthy subjects. Both markers demonstrated high diagnostic accuracy in differentiating FS from the other groups, suggesting they are promising diagnostic biomarkers for FS and support the role of neuroinflammation in FS development.
