Abstract
BackgroundThe immunologic findings that most consistently correlate with resistance in human schistosomiasis are high levels of IgE and low levels of IgG4. We have genotyped gene and promoter polymorphisms of cytokines associated with regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel (PZQ).Methodology/Principal FindingsIn this cohort, polymorphisms in IL-4 (−590T high IgE), IL-13 (−1055T high producer) and IFN-γ (+874A high producer) demonstrated several correlations with resistance to reinfection. Resistance to reinfection was significantly correlated with the heterozygous IL-4 −590 genotype C/T (OR 3.5, [CI 1.2, 10.2]) compared to T/T. Among men with a homozygous IL-13 genotype CC/TT, having a T allele at the IFN-γ +874 position increased the odds of resistance relative to individuals with the IFN-γ +874 A/A genotype (OR = 17.5 [CI 3.0, 101.5]). Among men with homozygous A/A IFN-γ genotype, the heterozygous IL-13 genotype C/T was associated with resistance relative to the homozygous C/C or T/T genotypes (OR = 22.5 [CI 3.5, 144.4]). No increases in odds of resistance were found in relation to the IL-13 genotype among those with a T allele in the IFN-γ gene or in relation to the IFN-γ genotype among those with a heterozygous IL-13 genotype. Calculation of the attributable proportion of resistance showed a significant synergistic interaction between IL-13 −1055 C/T and IL-4 −590 C/T.ConclusionsThe identified polymorphisms do not by themselves confer resistance or susceptibility, but we propose that these genotypes allow the resistant phenotype to be developed and expressed upon suitable immune exposure. Based on the literature, these polymorphisms contribute to the regulation of their respective cytokines, likely leading to downstream differences in the production and interrelationships of critical defense mechanisms.
Highlights
There have been many studies of resistance to schistosome infections in humans following treatment and reinfection
The identified polymorphisms do not by themselves confer resistance or susceptibility, but we propose that these genotypes allow the resistant phenotype to be developed and expressed upon suitable immune exposure
These polymorphisms contribute to the regulation of their respective cytokines, likely leading to downstream differences in the production and interrelationships of critical defense mechanisms
Summary
There have been many studies of resistance to schistosome infections in humans following treatment and reinfection. Of all the immunologic findings associated with these investigations, the most consistent observation is that resistance (usually defined as lower levels of infection) correlates with high IgE and low IgG4 antibodies against schistosome antigens [5,6,7,8,9,10,11,12,13,14,15,16,17,18]. These genes code for proteins that are associated with the regulation of Th2-type responses such as IL-3, IL-4, IL-5, IL-9, and IL-13 and IgE Polymorphisms in these cytokines that lead to an increase or decrease in cytokine levels could influence the antibody isotypes and cellular interactions that in turn may contribute to resistance or susceptibility of individuals to reinfection with schistosomiasis. We have genotyped gene and promoter polymorphisms of cytokines associated with regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel (PZQ)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
