The anti-larval IgE antibody response of adolescents with high or low resistance to infection by Schistosoma mansoni was evaluated before parasitological cure with oxamniquine and over an extended post-treatment period during which the least resistant subjects regained high infections. IgE from most sera, taken at several bleeding times before and after treatment, reacted, on immunoblots, with a large number of antigens (Ag) in schistosomular tegument extract. A family of 120-165-kDa cross-reacting molecules and a 85-kDa Ag were the most prominent Ag. Some of these determinants were shown to be located on the outer tegumental membrane and to be accessible to IgE on living larvae. The comparison of IgE between the two study groups showed that IgE levels were on average six-to eightfold higher (p less than 0.01) in the sera of the most resistant adolescents whereas there was no difference in patterns of Ag recognition between study groups. In contrast to IgE, anti-larval IgG and IgM levels were either similar in both groups or higher in the least resistant subjects when these exhibited high reinfection levels. IgG that competed for the binding of IgE to larval Ag were detected in most sera and their levels were higher in the least resistant group after reinfection. Finally, the treatment had no observable long-lasting effects on the levels and on the specificity of the anti-larval IgE. Altogether, these observations can be taken as evidence supporting a role of IgE in human resistance to infection by S. mansoni.

The hypothesis of an association between human resistance to reinfection by the parasite Schistosoma mansoni and anti-larval immunoglobulin isotypes was tested by logistic regression in the presence of the explicative variables water contact, age, and sex. Of the seven isotypes tested (IgM, IgG1, IgG2, IgG3, IgG4, IgA, and IgE), only IgE, IgG4, and IgG2 showed an association (positive for IgE and negative for IgG2 and IgG4) with resistance to reinfection after chemotherapy. The opposite effects of IgE and IgG4 were undissociable in the analysis, indicating that these isotypes probably antagonize each other in protection. The negative association of IgG2 with resistance is consistent with the view that anti-carbohydrate antibodies may facilitate reinfection. Finally, epidemiologic and immunologic studies support the view that there is a progressive but slow development of acquired immunity in children and adolescents.

A method allowing the immunopurification of human IgE from small volumes of sera with a yield close to 100% (mean = 97.8%; SEM = 0.7) has been developed. The immunopurification eluates were cleared of other class antibodies that could compete with IgE in specific assays. Immunopurification of IgE followed by specific IgE enzyme-linked immunosorbent assay (ELISA) (IMMEL) was then applied to sera of 160 individuals from an area endemic for Schistosoma mansoni. In comparison with radioimmunosorbent test (RAST) and ELISA performed on unfractionated sera, IMMEL provided the highest specific IgE signals. Furthermore, the best correlations between the specific IgE levels and either the specific basophil histamine release levels (r = 0.84; p less than 10(-4) or the anti-S. mansoni skin test values (r = 0.45; p = 10(-4)) were obtained with IMMEL. Measurement of anti-S. mansoni IgE levels in immunopurified fractions and in unfractionated sera of these 160 individuals revealed a strong serum inhibition (geometric means of 98.6% and 96.8% for the adult worms and the larvae, respectively) of the specific IgE reactivity in ELISA. This inhibition was correlated with the anti-adult worm and anti-larval IgG4 levels (r = 0.65; p less than 10(-4) and r = 0.58; p less than 10(-4), respectively). In contrast, this inhibition did not correlate with the specific IgG1, IgG2, IgG3 and IgM levels. Furthermore, the level of specific IgG4 was clearly lower than that of specific IgG1, suggesting that the major contribution of IgG4 in the competition effect is not due to higher levels but rather to a specificity spectrum close to that of the specific IgE. These results support the idea that a specific function of IgG4 in serum might be to control antigen recognition by IgE and consequently, to regulate anaphylactic reactions and IgE-mediated immunity.

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The design of programs for the control of endemies requires the knowledge of the principal factors that determine parasite transmission and infection levels in exposed populations. In the studies summarized in this article, the role of environmental and host specific factors in the infection by S. mansoni have been evaluated. It is shown that a limited number of factors actually influences infection intensity: water contacts, age, and sex were shown to account for 20 to 25% of infection variance, while 35 to 40% of it was accounted for by the effect of a major codominant gene. A remarkable fact is the important weighting (around 55% of the variance) of factors (the major gene and age) that influence human capacities of resistance. This observation strongly supports control measures aimed at increasing human resistance, such as vaccination. The effect of age on the development of resistance has now been observed in several studies on S. mansoni or S. haematobium. It is, therefore, a constant finding in schistosomiasis infections that resistance develops extremely slowly requiring a long period of exposure to the parasite and repeated infections. These studies provide strong incentives to increase efforts in the evaluation of the immune response of subjects living in endemic areas. Such evaluations are necessary to define vaccine and vaccination programs, and they are also urgently needed to evaluate the effects of chemotherapy on the development of immunity in children and adolescents, as well as on the persistence of protective immunity in adults. Immunological studies begin to provide a clearer picture of the role of acquired immunity in human protection against S. mansoni. It is increasingly clear that the slow development of resistance in children, as well as its alteration in certain age groups, are related to the maturation of parasite specific immunity and its alteration by specific immune factors. Thus, the development of resistance is associated with the maturation of IgE-dependent immunity, whereas blocking Ab may interfere in children and adolescents with the expression of full resistance. This finding raises the question as to whether a vaccine could include major allergens without triggering the well-known deleterious side effects associated with hypersensitivity reactions. The absence of such reactions in subjects with high parasite-specific IgE levels who are exposed to daily infections suggests that this may be feasible.

The nature of Ig receptors carried by lipopolysaccharide (LPS)-stimulated mouse spleen B cells was analyzed by surface iodination, direct antiserum precipitation and polyacrylamide gel electrophoresis. LPS activation led to a rapid decrease of surface IgD to 20 % and 80 % of the original level on days three and five of culture, respectively. Efficiency of iodination of cells doubled after culture but the proportional radioactivity in IgM reace of cells, but only in small amounts (1 % of total surface Ig) and this expression of IgG remained constant during 5 days of culture. We could definitively identify gamma-chains on the surface of cells, but only in small amounts (1% of total surface Ig) and this expression of IgG remained constant during 5 days of culture.

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