Antibody isotypes in human schistosomiasis mansoni.

Schistosoma mansoni-infected subjects from the Gezira Irrigated Area of Sudan were studied for serum immunoglobulin levels, and specific antibody titres to larval, adult and egg stage antigens, by class and IgG subclass. The 276 subjects were adult chronic cases (frequently exposed male canal cleaners), primary school children, and hospital-referred cases with acute symptoms including hepatosplenomegaly. Chronic untreated cases were compared with a similar group of canal cleaners 3 months after successful chemotherapy with Praziquantel administered at the start of the non-transmission season. All cases, except those previously treated, were egg positive at the time of blood sampling. Data from infected and treated cases were compared with measurements of serum immunoglobulin in a panel of European blood donors. The major findings are as follows: There is a consistently elevated total serum IgG concentration in infected groups which is accounted for mainly by an increased IgG1 subclass (greatest in chronic cases) and by a remarkable 10- to 11-fold increase in IgG4 in the untreated chronically infected group and in the schoolchildren. All infected groups showed high IgG antibody responses to all life cycle stage antigens, and IgM titres were high to adult and egg antigens in untreated canal cleaners. Major differences were evident in the distribution of IgG subclass antibodies between the infected groups: the response to larval and adult antigens is poor or absent in IgG1, IgG2 and IgG3 in untreated chronic infections but is high in IgG4, whereas in acute cases with hepatosplenomegaly and in school-children IgG1, IgG2 and IgG3 antibodies to larval antigens are in high titre but IgG4 and IgM responses to larvae are low or absent, the response in these isotypes being restricted in these cases to adult and egg antigens. Comparing the treated and untreated canal cleaners, although these are separate groups, the data suggest that Praziquantel reduces total serum IgA and IgM levels but has little effect on the raised IgG component except for the IgG4 subclass. The treated chronic cases show a reversal in the ratio of IgG1, IgG2 and IgG3 to IgG4 antibodies to larval and adult antigens compared with the untreated chronic group-the IgG4 response being low by 3 months after treatment and the IgG1, IgG2 and IgG3 being high. These data are discussed in relation to the possible importance of antibody isotype selection in determining host susceptibility to infection, with reference to age, exposure and treatment of the host.