Immune biomarkers for epilepsy in autism: indications of cytokine alterations in an exploratory cross-sectional pediatric study

Background Children with autism spectrum disorder (ASD) are at increased risk of epilepsy (EP), but distinguishing epileptic seizures from ASD-associated behavior remains a clinical challenge. Although previous studies have reported changes in peripheral immune markers in adults with EP, it remains unclear whether similar immune signatures are present in pediatric patients with both ASD and EP, and more pronounced than in children with ASD alone. Methods We conducted an exploratory, prospective, cross-sectional study of children aged 9–14 years with mild ASD, with or without EP, recruited from outpatient settings. Peripheral blood samples were analyzed by enzyme-linked immunosorbent assay for 23 immune proteins and by flow cytometry for leukocyte population counts. Analyses included t-tests / Mann–Whitney U-tests, post hoc tests for multiple comparisons, and effect size / power analyses. Results A total of 30 children were included, n = 21 with primarily mild ASD and n = 9 with mild ASD and EP. The epilepsy cases consisted of children with generalized seizures or self-limited epilepsy with centrotemporal spikes. Three immune proteins, Interleukin (IL)-12p70, IL-13 and IL-1β, were significantly increased in the ASD + EP group compared to the ASD-only group. However, the statistical power was low, and group differences did not remain significant after correction for multiple comparisons, even though effect sizes were moderate to large. No differences in the counts of activated leukocyte populations were observed. Conclusion These findings raise the possibility that immune system alterations may be associated with EP in children with ASD and could potentially aid diagnosis, although larger studies are needed to confirm these findings.