Immunochemical characterization and diagnostic potential of a 63-kilodalton Schistosoma antigen.
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Schistosoma circulating antigens were used for the detection of active infection. Anti-S. mansoni IgG2a monoclonal antibody (MAb) designated C5C4 was generated. The target epitope of this MAb was detected in adult worms, eggs, and cercariae antigenic extracts of S. mansoni and S. haematobium, had a molecular size of 63 kD, and was not detected in Fasciola hepatica and Ascaris. In addition, a 50-kD degradation product was identified only in the urine of infected individuals. Analysis by high-performance liquid chromatography of the purified antigen demonstrated only one peak. The 63-kD antigen was characterized as a protein containing 40.4% hydrophobic, 7.5% acidic, and 8.8% basic amino acids. The C5C4 MAb was used in a Fast Dot-ELISA for rapid and simple diagnosis of human schistosomiasis. The 63-kD circulating antigen was detected in 92% of urine samples from 330 S. mansoni-infected individuals, with 16% false-positive results among 130 noninfected individuals. (+info)
SR2 elements, non-long terminal repeat retrotransposons of the RTE-1 lineage from the human blood fluke Schistosoma mansoni.
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As in other eukaryotes, a substantial portion of the genome of the human blood flukes belonging to the genus Schistosoma appears to be composed of mobile genetic elements and other repetitive sequences. The constitutent elements and their relative organization are not well understood, although retroposons (the SM alpha elements) and a family of non-long terminal repeat (LTR) retrotransposons (the SR1 elements) have been reported from the genome of Schistosoma mansoni. Here, we report the presence of a second family of non-LTR retrotransposons from S. mansoni which we have termed the SR2 elements. SR2 elements are members of a recently described lineage of non-LTR retrotransposons typified by the RTE-1 non-LTR retrotransposon of Caenorhabditis elegans. We determined the sequence for approximately 3.9 kb of a consensus full-length SR2 element, which included a long 5' untranslated region (UTR), potential first and second open reading frames (ORFs) of 78 and 1,018 amino acid residues, respectively, a short 3' UTR, and an A-rich 3' terminus. SR2 elements were bound by target site duplications. The putative first and second ORFs did not overlap. The second ORF was homologous to retroviral pol and encoded an apurinic/apyrimidinic endonuclease and a reverse transcriptase. A number of extremely short SR2 elements of less than 0.5 kb, reminiscent of SINEs, were also characterized. These consisted solely of the 5' and 3' UTRs of full-length SR2 elements, having both ORFs deleted. Analysis indicated that these SINE-like SR2 elements were produced by replication of a SINE-like SR2 element, rather than by repeated deletions within larger SR2 elements. (+info)
Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen-specific cells.
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A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA). (+info)
The epidemiology of a recent focus of mixed Schistosoma haematobium and Schistosoma mansoni infections around the 'Lac de Guiers' in the Senegal River Basin, Senegal.
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A village with mixed Schistosoma mansoni and S. haematobium infections (probably in a early endemic phase) was identified around the Lac de Guiers in the Senegal River Basin. In documenting the epidemiology of both schistosomes, we focused on prevalence and intensity of infection, transmission patterns and the impact of treatment. S. mansoni prevalences (near 100%) and egg counts (overall geometric mean eggs per gram of faeces (epg) of 589 were high in all age groups, with 35% of individuals excreting > 1000 epg, and showing a slow decline in egg output only after the age of 30 years. The overall prevalence (28%) and egg counts (2% > 50 eggs/10 ml) of S. haematobium were low, with mean counts of 6.3 eggs/10 ml. Maximal mean S. mansoni egg counts were found in 5-9 year-old boys and in 15-19 year-old girls; S. haematobium maximal counts in 1-4 year-old boys and in girls aged 5-9. Extremely high Biomphalaria pfeifferi infection ratios were recorded over the whole year. Following a single treatment, re-infection was rapid with prevalences and mean egg counts of both Schistosoma species reaching pretreatment levels within 7 months. (+info)
TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine.
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C57BL/6 mice exposed to the radiation-attenuated schistosome vaccine exhibit high levels of protective immunity. The cell-mediated pulmonary effector mechanism involves IFN-gamma-producing CD4+ T cells in a focal response around challenge larvae. IFN-gamma can promote production of TNF and can synergize with this cytokine in its actions on responder cells. We have examined whether TNF plays a role in lung phase immunity to schistosomes using mice with a disrupted gene for TNFRI (TNFRI-/-). The most dramatic finding was that the schistosome vaccine elicited no protection whatsoever in these mice. However, this could not be attributed to a lack of responder cells, because more lymphocytes were lavaged from the airways of TNFRI-/- than wild-type mice. Furthermore, CD4+ T cells were equally represented in airway populations from the two groups and produced IFN-gamma upon Ag stimulation in vitro. In contrast, pulmonary macrophage function was defective in TNFRI-/- mice, as indicated by a failure to up-regulate inducible NO synthase mRNA. Histopathological analysis revealed that focal infiltrates were of similar size and cell composition in the two groups but that more parasites were free of foci in the TNFRI-/- mice. These animals had a greatly impaired IgG response to schistosomes, which may explain their lack of residual protection due to Ab in a situation where cell-mediated immunity is disabled. We suggest that the absence of protective immunity could result from a retarded build-up of leukocytes around migrating lung worms and/or a deficit in accessory cell function within a focus, both of which would permit parasite escape. (+info)
Familial resemblance in humoral immune response to defined and crude Schistosoma mansoni antigens in an endemic area in Brazil.
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This study addressed whether the humoral immune response to crude and defined Schistosoma mansoni antigens aggregates within families. The sample included 155 siblings from 42 nuclear families in Brazil. Sera examined by ELISA for antibody isotypes reactive to defined schistosome antigens and crude schistosome antigens (soluble adult worm antigen preparation and soluble egg antigen) demonstrated that there was a difference in sibling-pair correlations between defined and crude S. mansoni antigens. In contrast to the finding with crude antigens, egg-positive sibling pairs showed significant familial resemblance for all IgG subclasses and IgE to adult-stage antigens Smp20.8 and Smp50. Only the IgE and IgG4 isotypes showed familial resemblance to the egg-stage antigen, Smp40. Egg-negative sibling pairs showed significant familial resemblance only for IgE and IgG4 to Smp40. That both the IgE and IgG4 response to defined S. mansoni antigens showed familial resemblance is interesting in light of the converging evidence for the role of IgE and IgG4 in human susceptibility and resistance to reinfection. (+info)
Mice infected with Schistosoma mansoni generate antibodies to LacdiNAc (GalNAc beta 1-->4GlcNAc) determinants.
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Schistosoma mansoni is a parasitic trematode infecting humans and animals. We reported previously that adult S. mansoni synthesizes complex type biantennary N-glycans bearing the terminal sequence GalNAc beta 1-->4GlcNAc-R (lacdiNAc or LDN). We now report that mice infected with S. mansoni generate antibodies to LDN, as assessed by ELISA using a synthetic neoglycoconjugate containing LDN sequences. Sera of infected mice, but not uninfected mice, contained primarily IgM and low levels of IgG toward LDN. Interestingly, these antibodies also recognize bovine milk glycoproteins, which are known to express LDN sequences. The anti-LDN in sera of infected mice were affinity purified on immobilized bovine milk glycoproteins and shown to specifically bind LDN. An IgM monoclonal antibody (SMLDN1.1) was derived from the spleens of S. mansoni infected mice and shown to specifically bind LDN determinants. Immunoblots with affinity purified anti-LDN and SMLDN1.1 demonstrate that LDN sequences occur primarily on N-glycans of numerous glycoproteins of adult S. mansoni. LDN sequences are also expressed in many glycoproteins from S. japonicum and S. haematobium. The availability of antibody to LDN determinants should aid in defining the roles of these glycans in helminth and vertebrate biology. (+info)
Relationship between circulating antigen level and morbidity in Schistosoma mansoni-infected children evaluated by ultrasonography.
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Ninety-eight Schistosoma mansoni-infected children from an endemic area in Sharkia Governorate, Egypt were evaluated by abdominal ultrasonography to determine liver and spleen sizes, grade of periportal fibrosis, and splenic vein diameter. Circulating antigen levels were measured using a double sandwich ELISA in which the sensitivity was 91.8% and specificity was > 99%, with no evidence of cross-reactivity with other parasites. No significant relationship was observed between antigen level and clinical stages of the disease as assessed by physical examination (P > 0.05). When ultrasound was used to stage disease, the mean antigen level was significantly higher among hepatosplenic cases than intestinal cases (P < 0.05). No difference in mean antigen levels were found between the splenic and hepatic cases. Furthermore, a direct correlation (P < 0.01) was observed between antigen level and disease severity as monitored by ultrasonography. Antigen level showed a positive correlation with the degree of periportal fibrosis (P < 0.05). Moreover, a significant increase in the percent of children who were antigen positive (> 80 ng/ml) was found in those with more severe periportal fibrosis (P < 0.001). The findings suggest that ultrasonography along with measurement of circulating antigen levels predict morbidity in schistosomiasis mansoni. (+info)