A Study Of The Biomarker Of Schistosomiasis Japonicum And The Association Of Single Nucleotide Polymorphisms From Genes Of ST2 With Schistosomiasis Japonicum

Objective:Schistosomasis japonicum(S.japonicum)may cause life-threatening hepatosplenic and neurologic disease.However,diagnostic techniques with high sensitivity and specificity have been a prominent ob stacle for elimination of S.japonicum.We aimed to find a novel diagnosis method of S.japonicum in areas of low prevalence and low intensity of infection.Methods:Totally 837 participants lived in the S.japonicum-endemic area in Hubei province,C hina were enrolled and divided into the raining Set and Validation Set based on the chronolo,gical order of the samples collected,Among them,479 were infected with S.japonicum and 358 were exposed but non-infected according to Kato-Katz examination.Enzyme-linked immunosorbent assay(ELISA)assays were performed to detect the level of IgE,IgG4 antibodies specific for soluble S.japonicum worm antigenic protein(SWAP).Three algorithms(IgE score,IgG4 score and EGR score)for identifying the S.japonicum infection were generated in Training Set and subsequently validated and compared in Validation Set.The findings were replicated in an in dependent cohort from Brazil,an Schistosoma mansoni(S.mansoni)endemic area.Results:Infected individuals had higher levels of SWAP-specific IgQ IgG4 and IgE,and lower value of the IgE/IgG4 ratio than uninfected individuals in both the two Sets(p<0.01).Both the infected and uninfected individuals had a high prevalence of seropositivity for IgG.The predictive model EGR score performed best(area under the receiver operating characteristic(AUEC)C)0 905,sensitivity 82.7%;specificity 84.0%in the TS;AUROC 0.933,sensitivity 87.7%,specificity 89.1%in the VS)in China population.However,the predictive model IgG4 score performed best in Brazil population(AUROC 0.788,sensitivity 73.2%,specificity 73.3%).Conclusion:SWAP-specific IgG could be used as a biomarker for identifying individuals who have been previously exposed to S.japonicum,while the SWAP-specific IgE/IgG4 could be used as an immune biomarker for identifying S.japonicum infection in low prevalence and intensity endemic areas.Object:This study aims to explore the role of ST2 polymorphism playing in schistosomasis japonicum infection.Methods:We enrolled two cohorts from the endemic areas of schistosomasis japonicum.Jingzhou cohort had 947 participants including 339 end-stage schistosomiasis,307 chronic infections and 301 health controls,while Gongan cohort had 1166 participants including 300 end-stage schistosomiasis,299 chronic infections with stool negative,275 chronic infections with stool positive and 292 health controls.The levels of serum ST2 were detected with ELISA assays and the ST2 polymorphisms were detected by Taqman fluorescence probe.The correlation analysis was performed between the ST2 polymorphism and schistosomasis japonicum,the level of serum ST2 and SWAP-specific antibodies.Results:The ST2 polymorphism RS12712135?RS6543119?RS2110660?RS7568913?RS10179654?RS10178436 had significant difference between the end-stage schistosomiasis and chronic infections with stool positive(p<0.05),as well as between the chronic infections with stool negative and chronic infections with stool positive(p<0.05),and between the hronic infections with stool positive and healthy controls(p<0.05).Besides,all the above polymorphic sites were significant correlation to the levels of serum ST2(p<0.01).RS6543119 T increases the risk of developing into terminal schistosome hepatic disease(OR 1.17,95%confidence interval 1.00-1.36,p=0.048).There was no significant relation ship between the ST2 polymorphism and the SWAP-specific antibodies(p>0.05),but the SWAP-specific IgE antibody was significantly correlation to the level of serum ST2(effect size-0.084,p=0.002),Conclusion:Our results reported firstly that the ST2 polymorphism was significantly correlation to the schistosomasis japonicum and the schistosome hepatic disease,and the level of serum ST2 was significantly correlation to the SWAP-specific IgE antibody.Besides,we found 4 new ST2 polymorphic sites that have significant relationship with the levels of serum ST2.