RESUMEN
The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12⯵g/L (0.14-2.95) vs 1.79⯵g/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.
Asunto(s)
Proteína HMGB1 , Convulsiones Febriles , Humanos , Proteína HMGB1/sangre , Convulsiones Febriles/sangre , Masculino , Femenino , Lactante , Preescolar , Estudios de Seguimiento , Niño , RecurrenciaRESUMEN
BACKGROUND: The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce. METHODS: In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients' first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls. RESULTS: Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P < 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls. CONCLUSIONS: Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls. IMPACT: In patients with FSs, IL-1RA was higher following first FS than during febrile episodes without FSs and healthy periods after FSs. IL-1RA was higher in patients with FSs following first and recurrent FSs than in febrile controls. There was no significant difference in IL-1RA between febrile episodes of patients without FSs and febrile controls. Using IL-1RA as a surrogate marker of IL-1 axis activity, our results indicate that patients with FSs produced stronger inflammatory reactions during FS episodes but not during other febrile episodes or healthy periods after FSs. Cytokines may play a role in pathogenesis of FSs.