The Role Of Zinc α2 Glycoprotein In Serum And Cerebrospinal Fluid Of Epileptic Patients

Background and purpose:Epilepsy is one of the most common chronic nervous system diseases caused by the abnormal discharge of neurons.The pathogenesis of epilepsy is very complex,which is not clear at present.Epilepsy scientists have put forwad the hypothsis of ion channel,neural network abnormality,inflammation,neurotransmitter and immune mechanism,etc.In recent years,the mechanism of inflammation has attracted more attention.We also try to find a simple biomarker to promote the diagnosis,treatment and prognosis risk assessment of epilepsy,so as to reduce the burden of diagnosis and treatment brought by the disease.Researchers have detected the expression of zinc-α2-glycoprotein(ZAG)in cerebrospinal fluid(CSF)of Alzheimer’s disease,amyotrophic lateral sclerosis and other patients.ZAG has been found to play anti-inflammatory role in animal studies.ZAG over-expression can inhibit the increase of inflammatory factors such as tumor necrosis factor-a(TNF-α),interleukin-6(IL-6),transforming growth factor-β(TGF-β)and so on.Therefore,ZAG may play an anti-inflammatory role in epilepsy.We speculate that ZAG may play an active role in epileptic seizures,and ZAG in CSF or serum may be one of the biomarkers of epilepsy.Method:This study collected cerebrospinal fluid and blood of patients who were hospitalized in Henan people’s Hospital during 2017-2018 and voluntarily underwent lumbar puncture.A total of 100 people were included,79 of them were epileptic and 21 of them were Somatized.Enzyme linked immunosorbent assay was used to detect the level of ZAG in CSF and blood.Independent sample t test or Mann Whitney U test were used to analyze whether there was statistical difference in zag expression between the two groups;single factor analysis of variance or Kruskal Wallis h rank sum test were used to analyze and compare the data of multiple groups.Spearman correlation coefficient was used to analyze the correlation between the expression of ZAG and the age,course and frequency of epilepsy.The area under the ROC curve AUC and receiver operating characteristic curve ROC were used to evaluate the diagnostic value of ZAG in epilepsy.Result:1.The level of ZAG in CSF of epileptic patients was lower than that of control group,but in serum,the level of ZAG in epileptic patients was higher than that of control group,all of the above differences were statistically significant(P<0.05).2.CSF-ZAG in patients with epilepsy was positively correlated with age,HbAlc,ADA,CSF protein,serum ZAG and seizure age(P<0.05),negatively correlated with albumin and FT3(P<0.05).Multiple linear regression analysis showed that CSF protein and HbAlc were the main factors affecting CSF-ZAG level.Serum-ZAG was positively correlated with WBC and CSF-ZAG(P<0.05),and negatively correlated with albumin,HDL-C and CSF chloride<0.05).Multiple linear regression analysis showed that total protein and WBC were the main factors affecting serum ZAG level.3.In the analysis of epileptic subgroup,the level of serum and CSF ZAG in patients with encephalitis was higher than that in patients without encephalitis(P<0.05);the level of CSF and serum zag in patients with epileptic foci on MRI was significantly higher than that in patients without epileptic focus(P<0.05).4.ROC curve analysis was carried out to evaluate the diagnostic value of serum and CSF zag for epilepsy.The results were as follows:the area under ROC curve of CSF ZAG was 0.7086,the optimal threshold was 169.25ng/ml;the area under ROC curve of serum ZAG was 0.7354,the optimal threshold was 39.53 μg/ml,the differences were statistically significant.Conclusion:1.The level of ZAG in CSF and serum may be related to epileptogenic foci.2.CSF and blood ZAG may be one of the potential biomarkers for the diagnosis or differential diagnosis epilepsy.