BackgroundStudies in murine models and human populations have indicated that the collagen-rich granulomatous response against parasite eggs trapped in the liver is associated with the development of severe hepatosplenic schistosomiasis, characterized by periportal fibrosis and portal hypertension. The role of the humoral response in parasite susceptibility has been well established, but its participation in disease severity remains poorly understood. In this work, we evaluated the relationship between parasite-reactive IgE and IgG levels and schistosomiasis morbidity in infected patients with similar parasite burdens.Methodology/Principal FindingsNinety-seven Schistosoma mansoni-infected individuals were subjected to clinical examination and abdominal ultrasound analysis. IgG reactivity and IgE concentration against Schistosoma mansoni soluble egg antigens (SEA) and adult worm antigen preparation (SWAP) were evaluated by ELISA assay. Multivariable linear regression models were used to evaluate the relationship between parasite-reactive antibodies and the co-variables investigated. The study population showed low parasite burden (median 30 eggs/g feces), constant re-infection, and signs of fibrosis was detected in more than 30% of individuals. Most infected individuals showed IgG reactivity, and the median concentrations of IgE anti-SEA and anti-SWAP antibodies were 1,870 and 1,375 ng/mL, respectively. There was no association between parasite burden and antibody response or any parameter of disease severity. However, IgG anti-SWAP level was positively associated with morbidity parameters, such as spleen size and thickness of portal vein at the entrance and secondary branch. In contrast, the data also revealed independent inverse correlations between concentration of parasite-reactive IgE and gallbladder wall thickness, a marker of fibrosis in schistosomiasis.Conclusions/SignificanceThe data indicate that IgG anti-SWAP is positively associated with severe schistosomiasis, independently of parasite burden, while high production of parasite-specific IgE is associated with mild disease in the human population. Antibody profiles are good correlates for schistosomiasis severity and could be tested as biomarkers of disease severity.
Although there was a considerable discrepancy on fibrosis staging between examinations and a small power, transient elastography had an acceptable reproducibility in our population. Performance of at least 100 examinations should be used to define an experimented operator.
1 PAF injection into the rat paw is accompanied by the concomitant activation of NF-kB and neutrophil influx, which appears to be relevant to the up-regulation of kinin B 1 receptors. Herein, we analyse the role of TNF-a and IL-1b production for PAF-induced B 1 receptor upregulation in the rat paw. Additionally, we evaluate how cytokine production and neutrophil migration fit into the temporal sequence of events leading to PAF-induced B 1 receptor upregulation. 2 In our experiments, treatment with PAF resulted in a marked increase of B 1 receptor-mediated paw oedema and in situ production of TNF-a at 1 h and IL-1b at 3 and 6 h later. B 1 receptor-mediated paw oedema was significantly inhibited by anti-TNF-a antibody and by interleukin-1 receptor antagonist (IRA). 3 TNF-a was necessary for the local PAF-induced IL-1b production. NF-kB blocker PDTC prevented the production of both TNF-a and IL-1b, indicating that cytokine production is NF-kB dependent. 4 Depletion of neutrophils with an anti-PMN antibody prevented IL-1b, but not TNF-a, production. Although both TNF-a and IL-1b are relevant to functional B 1 receptor upregulation, PAF-induced increase in B 1 receptor mRNA was markedly suppressed by anti-TNF-a and, to a lesser extent, by IRA. B 1 receptor mRNA expression was also prevented by the anti-PMN antibody. 5 In conclusion, the activation of the TNF-a/neutrophil axis by PAF seems to be sufficient for B 1 receptor mRNA production. However, the TNF-a/neutrophil axis is also necessary for IL-1b production. These two processes might lead to the appearance of functional kinin B 1 upregulation receptors in vivo after PAF treatment.
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