title: Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender.
abstract: Schistosoma mansoni infection is highly endemic in parts of Uganda, and periportal fibrosis is common in communities along the shore of Lake Albert. In this study, we have identified cellular immune responses associated with fibrosis. A cohort of 199 individuals aged 6-50, resident in the village for at least 10 years or since birth, were examined for evidence of periportal fibrosis by ultrasound using the Niamey protocol. Whole-blood samples were assayed for levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF-alpha, IFN-gamma, IL-1beta, and RANTES) in the absence of in vitro Ag stimulation, and after stimulation with egg and worm Ags. A lack of Ag specificity allowed the number of variables in the analysis to be reduced by factor analysis. The resulting factor scores were then entered into a risk analysis using a classification tree algorithm. Children, adult males, and adult females had different factors associated with fibrosis. Most cases of fibrosis in children (eight of nine) were associated with low (<47th percentile) IL-10 factor scores. Adult females at lowest risk had relatively high IFN-gamma factor scores (>83rd percentile), whereas those at highest risk had a combination of intermediate (32nd to 83rd percentile) IFN-gamma and relatively high (>60th percentile) TNF-alpha factor scores. Adult males at lowest risk of fibrosis had moderate TNF-alpha factor scores (55th to 82nd percentile), and a high risk was associated with either high TNF-alpha factor scores (>82nd percentile), or intermediate TNF-alpha combined with low RANTES factor scores (<58th percentile). These results demonstrate that periportal fibrosis is associated with cytokine production profiles that vary with both age and gender.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. mb350@cam.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Booth
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Mwatha
authors.forename: Sarah
authors.initials: S
authors.lastname: Joseph
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: Hilda
authors.initials: H
authors.lastname: Kadzo
authors.forename: Edmund
authors.initials: E
authors.lastname: Ireri
authors.forename: Frances
authors.initials: F
authors.lastname: Kazibwe
authors.forename: Jovanice
authors.initials: J
authors.lastname: Kemijumbi
authors.forename: Curtis
authors.initials: C
authors.lastname: Kariuki
authors.forename: Gachuhi
authors.initials: G
authors.lastname: Kimani
authors.forename: John H
authors.initials: JH
authors.lastname: Ouma
authors.forename: Narcis B
authors.initials: NB
authors.lastname: Kabatereine
authors.forename: Birgitte J
authors.initials: BJ
authors.lastname: Vennervald
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism*; D002648:Child; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000145:classification / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008109:Liver Diseases, Parasitic / Q000145:classification / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D018570:Risk Assessment; D012555:Schistosomiasis mansoni / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000947:Antigens, Helminth; D018946:Chemokine CCL5; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma