Circulating high mobility group box-1 and toll-like receptor 4 expressions increase the risk and severity of epilepsy

Abstract

This study aimed to investigate the association of serum high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) expressions with the risk of epilepsy as well as their correlations with disease severity and resistance to anti-epilepsy drugs. One hundred and five epilepsy patients and 100 healthy controls (HCs) were enrolled in this case-control study, and serum samples were collected from all participants to assess the HMGB1 and TLR4 expressions by enzyme-linked immunosorbent assay (ELISA). Both serum HMGB1 (P<0.001) and TLR4 (P<0.001) expressions were higher in epilepsy patients than in HCs, and they displayed good predictive values for risk of epilepsy. Moreover, HMGB1 was positively correlated with TLR4 level (r=0.735, P<0.001). HMGB1 and TLR4 levels were both elevated in patients with an average seizure duration >5 min compared to patients with a seizure duration ≤5 min (P=0.001 and P=0.014, respectively). Also, HMGB1 and TLR4 were increased in patients with seizure frequency >3 times per month compared to patients with seizure frequency ≤3 times per month (both P=0.001). In addition, HMGB1 and TLR4 expressions were higher in intractable cases compared to drug-responsive cases (P<0.001). In conclusion, both HMGB1 and TLR4 expressions were correlated with increased risk and severity of epilepsy and their level was higher in patients resistant to anti-epilepsy drugs.

Evaluation of serum high‐mobility group box 1 concentration in dogs with epilepsy: A case‐control study

“…However, Results of the present study are in line with a previous report about human patients with epilepsy showing higher serum HMGB1 concentration in the epilepsy group than in the healthy control group. 18 Receiver operating characteristic curve analyses in the present study supported the assertion that serum HMGB1 concentration could be a biomarker for canine epilepsy. The cutoff value for serum HMGB1 concentration was determined as 0.15 ng/mL, as it exhibited the highest sensitivity (82.1%) and specificity (65.4%) for predicting canine epilepsy.…”

“…29 Furthermore, it has been demonstrated that the elevation of serum HMGB1 concentration is related to epilepsy in human patients. 18 Therefore, considering the previously reported results and our results, which showed that serum HMGB1 concentration was increased in epileptic dogs, analysis of HMGB1 in serum might be more suitable than that in CSF in epileptic dogs. However, Results of the present study are in line with a previous report about human patients with epilepsy showing higher serum HMGB1 concentration in the epilepsy group than in the healthy control group.…”

“…Both delta and ratio were found to be unrelated to the duration of treatment (Figure 4). [15][16][17][18] It was recently confirmed that the expression of TLR-4 signaling cascade including HMGB1 was higher in the brain tissue of dogs with epilepsy than in normal dogs. 14 serum.…”

“…dogs with a seizure frequency of ≤3 times/month and dogs with a seizure frequency of >3 times/month. 18 Well-controlled status was defined as the occurrence of <1 seizure/month after the initiation of epilepsy treatment. 28 Poorly controlled status was defined as the occurrence of >1 seizure/month.…”

“…[15][16][17] Furthermore, an elevation of serum HMGB1 level is associated with an increase in seizure duration, seizure frequency, and antiepileptic drugs resistance in human epileptic patients. 18 There are several reports on the correlation between serum HMGB1 levels and certain diseases in dogs, such as lymphoma, systemic inflammatory response syndrome, gastric dilatation and volvulus, and pancreatitis [19][20][21][22][23] ; however, among the cerebral diseases of dog, encephalitis is the only disease that correlated with HMGB1 levels in CSF. 24 This study aimed to establish preliminary support for the use of serum HMGB1 concentration as a potential biomarker for epilepsy in dogs.…”