Zmienione procesy zapalnych w mózgu i specjalne cząsteczki regulacyjne u pacjentów z epilepsją idiopatyczną uogólnioną w zależności od zakażenia pasożytem Toxoplasma gondii

AIM: To investigate inflammatory signaling pathways and regulatory microRNA expression profiles in patients with idiopathic generalized epilepsy according to Toxoplasma gondii serostatus. The novelty of this study lies in the integrated evaluation of the HMGB1-TLR4-RAGE-IRAK-TRAF6-NF-κB signaling axis together with selected regulatory microRNAs across groups stratified according to both epilepsy diagnosis and T. gondii serostatus. METHODS: A total of 40 participants aged 18-50 years were enrolled and classified into four predefined groups (n = 10 each): control [epilepsy (-)/T. gondii (-)], epilepsy [epilepsy (+)/T. gondii (-)], T. gondii [epilepsy (-)/T. gondii (+)], and epilepsy + T. gondii [epilepsy (+)/T. gondii (+)]. Serum concentrations of HMGB1, NF-κB, TLR4, TNF-α, TRAF6, RAGE, and IL-1β were measured using ELISA. Plasma expression levels of HMGB1, IL1B, IL10, IRAK1, IRAK2, TLR4, TNFA, and RAGE mRNAs, as well as miR-146a, miR-155, miR-26b, and miR-106b, were determined by quantitative real-time PCR. Group comparisons were performed using the Kruskal-Wallis test, and associations between variables were evaluated using Spearman correlation analysis. RESULTS: IL1B gene expression was significantly increased in the T. gondii group compared with the epilepsy and epilepsy + T. gondii groups (p < 0.05), whereas HMGB1 gene expression was significantly lower in the T. gondii group than in the other study groups (p < 0.05). IRAK2 expression was significantly elevated in the epilepsy + T. gondii group compared with controls (p < 0.05). Serum HMGB1 levels were higher in the T. gondii group [5.87 (3.42-8.69)] than in the epilepsy group [3.10 (2.70-6.70)], and serum TNF-α levels were similarly higher in the T. gondii group [279 (83.47-416.57)] than in the epilepsy group [79 (28-279)] (p < 0.05). Among the investigated microRNAs, plasma miR-155 expression was higher in the T. gondii group [4.50 (2.50-9.51)] than in the control [1.26 (0.23-2.67)] and epilepsy [3.36 (0.63-5.81)] groups, whereas miR-106b expression was lower in the epilepsy group [2.42 (0.07-3.99)] than in the other study groups (p < 0.05). Correlation analyses demonstrated significant associations among components of the HMGB1-TLR4-NF-κB inflammatory signaling pathway and selected regulatory microRNAs. CONCLUSION: The findings of this exploratory study demonstrate differences in selected inflammatory signaling components and regulatory microRNA expression profiles across groups defined by idiopathic generalized epilepsy and T. gondii serostatus. In particular, significant alterations were observed in IL1B, HMGB1, IRAK2, miR-155, and miR-106b expression, together with differences in serum HMGB1 and TNF-α levels. However, given the small sample size, cross-sectional design, and predefined group allocation, these findings should be considered exploratory and do not establish a causal relationship between T. gondii infection and epilepsy. Larger prospective studies are required to determine the clinical and pathophysiological significance of these molecular alterations.