title: Carriage of DRB1*13 is associated with increased posttreatment IgE levels against Schistosoma mansoni antigens and lower long-term reinfection levels.
abstract: Praziquantel treatment for Schistosoma mansoni infection enhances Th2 responsiveness against parasite Ags, but also increases the variance in Ab isotype levels. This effect may arise partly from genetic heterogeneity. In this study, associations between HLA polymorphisms at three loci (HLA-DQB1, HLA-DQA1, and HLA-DRB1) and posttreatment Ig responses to S. mansoni Ags were assessed in 199 individuals aged 7-50 years from Uganda. Blood samples were assayed for IgG1, IgG4, and IgE levels against soluble worm Ag (SWA), soluble egg Ag, tegument Ag, and a recombinant tegumental Ag (rSm 22.6) 7 wk after treatment. Multivariate ANOVA analysis initially revealed associations between carriage of DRB1*13 and increased levels of IgG1, IgG4, and IgE against SWA, tegument Ag, and rSM22.6. Subsequent analysis of covariance, which controlled for correlations between isotype levels and also included pretreatment IL-4, IL-5, and IL-13 responsiveness against SWA as covariates, revealed an independent association only between DRB1*13 and a factor score summarizing IgE levels to worm-derived Ags, which was strongest in adults. A post hoc age- and sex-stratified analysis revealed lower reinfection intensities at 1 year, 22 mo, and 6 years after the first round of treatment among carriers of DRB1*13. These results indicate that genetic background has a prominent influence on the posttreatment Th2 immune response to S. mansoni Ags, as well as a downstream association with long-term reinfection levels.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom. mb350@cam.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Booth
authors.forename: Marie A
authors.initials: MA
authors.lastname: Shaw
authors.forename: Danielle
authors.initials: D
authors.lastname: Carpenter
authors.forename: Sarah
authors.initials: S
authors.lastname: Joseph
authors.forename: Narcis B
authors.initials: NB
authors.lastname: Kabatereine
authors.forename: Henry C
authors.initials: HC
authors.lastname: Kariuki
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Mwatha
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: Brigitte J
authors.initials: BJ
authors.lastname: Vennervald
authors.forename: John H
authors.initials: JH
authors.lastname: Ouma
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000097:blood*; D000947:Antigens, Helminth / Q000276:immunology*; D002648:Child; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010270:Parasite Egg Count / Q000706:statistics & numerical data; D011223:Praziquantel / Q000627:therapeutic use; D012008:Recurrence; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012552:Schistosomiasis / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology
chemical_list: D000871:Anthelmintics; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C506473:HLA-DRB1*13 antigen; D007073:Immunoglobulin E; D011223:Praziquantel