title: Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses.
abstract: Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Burke
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Magda K
authors.initials: MK
authors.lastname: Ellis
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Candy
authors.initials: C
authors.lastname: Chuah
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: Ramm
authors.affiliation: Hunan Institute of Parasitic Diseases,WHO Collaborating Centre for Research and Control of Schistosomiasis in the Lake Region,China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: QIMR Berghofer Medical Research Institute,Brisbane,Qld 4006,Australia.
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002908:Chronic Disease; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology*; D015398:Signal Transduction; D015854:Up-Regulation; D055815:Young Adult
keywords: Schistosoma; Schistosomiasis; clinical; hepatic fibrosis; liver; transcriptomics