Serumexpressionof Free IL-18 In Neuropsychiatric Lupus Patients And Analysisofrelated Risk Factors

BackgroundSystemic lupus erythematosus(SLE),which has a striking female predominance,is a chronic systemic autoimmune inflammatory disease.SLE with central or peripheral nervous system manifestations is known as neuropsychiatric systemic lupus erythematosus(NPSLE),including seizure,cerebral vascular disease,psychosis,etc.Interleukin(IL)-18,a member of IL-1 family,is a proinflammatory cytokine which can be activated after being cleaved by caspase-1.IL-18 binding protein(IL 18-BP),being a readily secreted protein,belongs to shed soluble receptor category.IL-18BP can bind to IL-18 thus downregulating its activity.However,IL-18 and IL-18BP levels in NPSLE and its subtypes are still not known.Objective:The aim of this article is to explore whether the interplay between IL-18 and its natural inhibitor IL-18BP plays any role in NPSLE and its subtypes,and to analyze the risk factors of NPSLE so as to find potential diagnostic targets for NPSLE,which is beneficial to its early treatment and better prognosis.MethodsData from 137 SLE patients and 30 healthy controls(HC)were consecutively collected from January,2020 to March,2021.Serum levels of total IL-18 and IL-18BP for all patients and HC were measured by enzyme linked immunosorbent assay(ELISA).Free IL-18 was calculated based on the law of mass action.Firstly,we divided SLE patients into active group and quiescent group based on SLEDAI-2k.Disease states were classified as either being quiescent(SLEDAI-2k≤4)or active(SLEDAI-2k>4)and serum levels of IL-18,IL-18BP and free IL-18 were compared between HC and SLE groups.In addition,correlations between these three parameters and SLE disease activity were analyzed.Patients in the active group were then classified into NPSLE group and non-NPSLE group.We then apply binary logistic regression analysis on the significant variables between NPSLE group and non-NPSLE group.Also,NPSLE patients were divided into seizure group and non-seizure group,cerebrovascular disease group and non-cerebrovascular disease group or psychosis group and non-psychosis group.Concentrations of IL-18,IL-18BP and free IL-18 were compared between different groups.ResultsAmong the 13 7 SLE patients,103 had active disease and 34 had quiescent disease.Serum levels of free IL-18 were significantly higher in active SLE patients than in HC and quiescent SLE patients(p=0.0001),and were correlated with disease activity(r=0.268,p=0.002).Also,serum free IL-18 levels were increased in NPSLE patients(p=0.0079).We found that elevation of free IL-18 and platelet(PLT)and decrease of IgG are risk factors for NPSLE by binary logistic regression analysis and the area under the ROC curve(AUC(95%CI))is 0.802(0.717-0.887)for the predicted probability,which is higher than that of free IL-18(0.633(0.523-0.743)),PLT(0.647(0.540-0.743))or IgG(0.663(0.556-0.770)).In the meantime,serum free IL-18 levels in NPSLE patients with seizure disorders were significantly higher than that in those with other neuropsychiatric symptoms(p=0.0439),while IL-18 and IL-18BP levels were comparable.Of the 16 patients with seizure disorders,11 patients suffered from generalized seizures and the rest 5 patients had focal onset.Serum levels of IL18 and IL-18BP were not statistically different between different seizure onset groups,while free IL-18 levels were significantly higher in generalized onset group(p=0.0115).Within the 50 NPSLE patients,17 had cerebrovascular disease and 9 had psychosis.Although serum IL-18BP concentration in cerebrovascular disease group were lower than that in non-cerebrovascular disease group(p=0.0358),IL-18 and free IL-18 levels were not significantly different.What’s more,serum IL-18,IL-18BP and free IL-18 were similar between psychosis group and non-psychosis group.ConclusionsThe serum expression of free IL-18 was correlated to activity of SLE and significantly increased in NPSLE patients,especially in those with NPSLE related seizures.Moreover,elevation of free IL-18 and PLT and decrease of IgG were risk factors for NPSLE.In this regard,free IL-18 may be a potential diagnostic target for NPSLE.