Antibody isotypes of immune complexes in schistosomiasis mansoni in Sudan

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Abstract
Summary From a panel of monoclonal antibodies to Schistosoma mansoni, one that is specific to a shared cercarial and schistosomular antigen, and does not react with other major parasite species including Fasciola hepatica, was selected for use as an antigen‐capture layer in a sandwich ELISA for detection of specific circulating immune complexes in the blood of S. mansoni‐infected subjects from Sudan. The test, which identifies immune complexes of only a single antibody‐bound antigen, is developed using human Ig class‐ and IgG subclass‐specific enzyme (HRP)‐antibody conjugates. European blood donor sera and those with rheumatoid factor and/or anti‐nuclear antibody are negative in this test. The prevalence and distribution of the different antibody isotypes in antigen‐specific complexes was determined in 276 subjects of four infection groups; primary school children, adult irrigation canal cleaners with chronic infections, an equivalent group of Praziquantel cured canal cleaners, and hospital‐referred cases with severe hepatosplenic symptoms. The isotype profiles of antibodies in the specific complexes were compared with those in the total serum complexes prepared by polyethylene glycol precipitation. In chronic infections and in children there is a high prevalence of IgG and IgM specific complexes, the IgG being predominantly IgG1, with little or no IgG3 and IgG4. Treated chronic infections show reduced specific complexes in all classes of antibody. Compared with chronic and children's infections, a large proportion of the patients with severe infections have in addition to high IgM, high levels of IgG2, IgG3 and IgG4 specific complexes, a fact which suggests a causal relationship between antibody production in one or more of these subclasses to the circulating antigen and symptoms of hepatosplenic disease. Although all subjects have significant amounts of total serum complexes with IgG, untreated chronic infections have much higher concentrations than other infected groups. This group also has the highest levels and prevalence of IgM and IgE complexes. In treated chronic cases IgG and IgM total complexes are greatly reduced. The significant finding in patients with severe symptoms is the relatively high IgA immune complex level compared with other groups. Taken overall the results suggest that screening of populations in endemic regions for serum immune complexes by specific and non‐specific means could offer valuable data on the significance of antibody responses to circulating antigens in different isotypes in relation to pathogenesis. In addition the loss of complexes after chemotherapy may be of special value in determining the success of treatment regimens.