Therefore, high IgG4 production, which may be more than 100-fold higher than IgE antibodies, can interfere with the detection of parasite-specific IgE . 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/Significance The data indicate that IgG anti-SWAP is positively associated with severe schistosomiasis, independently of parasite burden, while high production GDC-0084 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. Introduction is the most prevalent species of the genus infecting human beings. Infection with this organism causes intestinal and hepatic schistosomiasis in more than 100 million individuals that primarily live in sub-Saharan Africa, the Caribbean and South American areas, including Brazil C. In endemic areas of egg deposition induces a type-2 immune response, which is characterized by the production of IL-4, IL-5 and IL-13 cytokines that, in addition to IL-10, GDC-0084 has been associated with the down-modulation of the initial type-1 immune response and granuloma formation C. In experimental models, these type-2 cytokines, particularly IL-13, have been associated with fibrogenesis and therefore with severe pathology , C. In humans, the regulation of liver fibrosis during schistosomiasis may be even more complex, with multiple mediators regulating disease progression. Epidemiologic studies Rabbit Polyclonal to LRG1 have indicated that infected patients presenting with severe fibrosis have elevated levels of the chemokine CCL3 , , tumor necrosis factor (TNF)-alpha, IL-5 and IL-13 C, whereas patients with low levels of fibrosis present with high levels of IFN-gamma and IL-10 , . Association of Th2-biased cytokine responses with persistent hepatic fibrosis and its persistence after treatment were also identified in infected patients from the Philippines . In contrast to the amount of knowledge about the role of cytokines in granuloma formation and their association with disease severity, the participation of antibody responses against contamination on the progression of clinical disease has been poorly investigated. The importance of B cell and antibody responses in the pathology associated with schistosomiasis has been suggested from experimental infections of in B cell-deficient mice , . In human populations, immunoepidemiologic studies have indicated that increased levels of anti-schistosome IgE are closely correlated with resistance to re-infection and that high levels of anti-schistosome IgG4 are correlated with increased susceptibility to the parasite , . In contrast, there are very few clinical studies showing the relationship between specific antibody production and schistosomiasis severity. These studies have exhibited a positive association between anti-schistosome IgG responses, particularly IgG4, and severe schistosomiasis , . To better understand the role of antibody response in the pathology of schistosomiasis, we first quantified IgE concentration and then evaluated the association of parasite (SEA and SWAP)-reactive IgG and IgE with the clinical form of the disease, which was defined based on clinical and ultrasound examination of contamination received specific treatment (a single dose of oxamniquine at 15 mg/kg for adults and GDC-0084 20 mg/kg for children, since the treatment recommended by Brazilian authorities at the time of the diagnosis), and other diagnosed diseases were treated or directed for specialized treatment. To obtain antigens used in the experiments mice were experimentally infected as detailed in antigen preparation. All animal procedures were approved by the animal-care ethics committee of the Federal University of Minas Gerais (Protocol # 158/2008) and were GDC-0084 performed under the guidelines from COBEA (Brazilian College of Animal Experimentation) and strictly followed the Brazilian legislation for Procedures for the Scientific Use of Animals (11.794/2008). Study Population The subjects used in.