Antibody isotype responses to egg antigens in human chronic Schistosomiasis mansoni before and after treatment

Abstract

In the present communication we analyzed the levels of IgG1, IgG2, IgG3, IgG4 and IgE Analysis of antibody responses to diferent antigens in patients' sera shows that the slow development of immunity to reinfection after treatment of Schistosoma infection is partially atributable to the continued presence of blocking antibodies in susceptible individuals, particularly IgG4 and IgG2 (Demeure et al. 1993). The role of IgE in several imune mechanisms against the parasite has been described in vitro, suggesting that these mechanisms might be involved in protection against human schistosomiasis (Capron et al. 1999). The levels of IgE antibodies to S. hematobium, mainly against adult worms, increased progressively with the age of the patient and were related to resistance to reinfection after chemotherapy (Hagan et al. 1991). The influence of IgE in immunity to S. mansoni reinfection has also been reported by other authors (Dunne et al. 1992, Rihet et al. 1992, Demeure et al. 1993.We have previously evaluated the influence of antibodies of the isotypes IgE and IgG4 on the resistance and susceptibility to infection by S. mansoni in human populations living in two contiguous endemic villages (Itapinassu and São Joaquim) in Northeast Brazil by using soluble egg antigen (SEA) and soluble worm antigenic preparations (SWAP) in a immunenzymatic assay (ELISA). An association between age and levels of IgE schistosome-specific antibodies was found. The age-IgE profile followed that expected for an antibody involved in resistance to infection (Gomes et al. 1998 In the present communication we extended our previous studies, analyzing the levels of IgG1, IgG2, IgG3, IgG4 and IgE isotypes to SEA, in 58 patients from São Joaquim village, in order to evaluate the patterns of antibodies responses before and after treatment. The procedures followed were in accordance with the ethical standards on human experimentation.Parasite burden was measured in stool specimens by the Kato-Katz method, and water contacts were evaluated by a specific questionary. Blood was obtained by venipuncture, before treatment and six months after treatment with oxamniquine (15 mg/kg for adults and 20 mg/kg for patients under 15 years old), and serum stored at -20 o C until use. SEA was obtained using standard procedures (Gazzinelli et al. 1983). This preparation was dialyzed against distilled water and the protein concentration determined by the method of Lowry et al. (1951). IgG1, IgG2, IgG3, IgG4 and IgE antibody response to SEA was evaluated by ELISA (Hagan et al. 1991) using mouse monoclonal anti-human IgG1, IgG2, IgG3, IgG4 and IgE (Fc fragments). Assays were developed using horseradish peroxidase-conjugated rabbit anti-mouse IgG. Statistical analysis was performed using the software EPIINFO V 6.04.Before treatment, IgE and IgG4 anti-SEA antibody levels were more elevated than IgG1, IgG2, and IgG3 (Fig. 1). These antibody levels tended to increase after treatment (Fig. 2) suggesting stimulation of the antibody response due the drug effects or antigens e...

Protective immunity to Schistosoma haematobium infection is primarily an anti-fecundity response stimulated by the death of adult worms

“…The finding that dying worms provide the main source of protective antigen fits with several studies showing that praziquantel treatment, which kills adult schistosomes but has little effect on immature worms (23), can boost antibody responses associated with protection against reinfection (20,24). The finding that protective immunity is likely to principally target fecundity is supported by the findings that lower levels of S. haematobium egg output were found relative to levels of circulating anodic antigen (a marker for worm burden) in adults than in children (25), and that S. haematobium fecundity is reduced by the immune response in mice (26).…”

Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases

“…This correlates with the age-dependent development of human immunological resistance to reinfection with S. mansoni , which is also associated with the presence of anti-tegument IgG antibodies (Karanja et al, 2002). In addition, it has been proposed that the resistance to re-infection following chemotherapy with praziquantel, is mediated by antibodies specific to schistosome antigens released upon worm death that are not normally encountered by the host immune response (Mutapi et al, 1998; Gomes et al, 2002). These observations prompted searches to identify those molecules recognized by antibodies taken from RA cercariae-vaccinated mice, or humans resistant to re-infection.…”

Development of a Specimen-Sparing Multichannel Bead Assay to Detect Antiparasite IgG4 for the Diagnosis of Schistosoma and Wuchereria Infections on the Coast of Kenya

“…In summary, although the level of antiparasite IgG4 tends to peak in younger age groups, it is also found to be elevated in active Schistosoma infections among adults. 40,48 In our evaluation, although our sampling strategy and small sample size of the triple test group did not allow for a breakdown of the test characteristic analysis by age, it does not seem that IgG4 positivity differed greatly depending on age in those participants positive for S. haematobium infection by egg counting (Table 4). Furthermore, age distribution was fairly uniform across both the ELISA subset and the group as a whole.…”

“…24,28,44,45 Whereas studies have shown lower IgG4 levels in lighter infections, the correlation between IgG4 positivity and infection status is high (with greater than 90-95% positivity in infected subjects), making it a useful marker for current infection. 26,39,40,46 Treatment effects on antischistosome IgG4 have been varied across studies and can be difficult to interpret given the possibility of reinfection, differences in methodology, and the ideal time post-treatment to test. 45 Grogan and others 28,47 showed a persistence of IgG4 levels against Schistosoma adult worm antigens in both adults and children 5 weeks and 2 years after treatment, whereas IgG4 levels against egg antigens declined in all groups at these intervals post-treatment.…”

“…39 In past studies, sensitivity for diagnosing Schistosoma infection using SWAP (by ELISA for total IgG) has been shown to be comparable with sensitivity using soluble egg antigens. 39,40 Multichanneled fluorescent antibody detection assay. SWAP antigen (crude extract) was provided courtesy of the laboratory of Christopher King (Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH).…”