IgE and cells in schistosomiasis.
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Biomedical subjects
Publications and source records attributed to M Capron.
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Levels of IgG, IgE, IgM, and IgA were determined, specific antibodies were detected by the fluorescent antibody test, hemagglutination test, complement fixation test and immunoelectrophoresis, and intradermal tests for delayed hypersensitivity to Schistosoma mansoni antigens were performed in Brazilian patients with schistosomiasis mansoni. The results were compared according to the clinical forms of the disease. IgG levels and antibody titers increased progressively in the subclinical, hepatomegalic, and hepatosplenic forms and there was a statistical relationship between IgG levels and the intensity of responses to the four serological tests; Delayed hypersensitivity (DHS) was found more frequently in hepatosplenic patients and more particularly in those with splenomegaly. DHS also correlated with age, but not with sex or with skin color. The strongest DHS reactions were observed in patients 20 to 34 years old, and in those having the highest fecal egg output. IgG levels, antibody titers, and DHS responses decreased after splenectomy and portal filtration of the worms. No significant variation was observed between untreated subjects, patients who were splenectomized and a group not subject to reinfection for 4 yearsk0
Specific IgE antibodies from immune rat serum were demonstrated to mediate the immune adherence of normal rat macrophages to Schistosome mansoni schistosomules, which was followed by a cytototoc action. Hence, a new positive role of IgE antibodies in protective immunity is argued.
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Schistosomiasis is a parasitic infection of man which is widespread in tropical countries, and which so far has resisted attempts at control. We have been approaching the problem from an immunological angle. We have previously reported the production of a rat monoclonal IgG2a antibody against Schistosoma mansoni which exhibits marked cytoxicity for schistosomula in the presence of eosinophils and a high degree of protection by passive transfer in naive rats. This antibody, IPLSm1, was shown to bind specifically to a schistosomulum membrane target antigen defined as a glycoprotein of relative molecular mass 38,000 (38K), which is strongly immunogenic in schistosome infection of various animal species including man. Although theoretically the 38K protein represents an excellent candidate for a potential vaccine against schistosomiasis, the glycanic nature of the epitope recognized by IPLSm1 limits its production by DNA recombinant technology. It was, moreover, shown that, together with protective antibodies, the 38K molecule was able to induce the production of blocking IgG2c antibodies that inhibit the functional properties of IPLSm1 both in vitro and in vivo. Therefore, following Jerne's network theory, we considered an alternative approach, the possibility of immunization using anti-idiotype antibodies. In the present study, rat monoclonal anti-idiotype antibodies were produced against IPLSm1 (AB1). Anti-idiotype antibodies (AB2) were selected by their capacity to inhibit the binding of radioiodinated AB1 to its 38K target antigen. Sera from naive LOU rats immunized with a purified AB2 preparation contained specific anti-schistosome antibodies (AB3) which bound to 38K. AB3 antibodies were strongly cytotoxic for schistosomula in the presence of rat eosinophils and conferred highly significant protection by passive transfer. Most importantly, rats immunized with AB2 demonstrated marked protection (50-80%) to a challenge infection.
The complementary DNA sequence encoding the Mr 28,000 antigen of Schistosoma mansoni has been isolated and expressed in Escherichia coli. Experimental vaccination of rats, hamsters and monkeys with a recombinant fusion protein induces a strongly cytotoxic antibody response. Immunization of rats and hamsters with this protein leads to significant protection against a natural challenge infection with live cercariae.