Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection

Abstract

Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection.

Ascaris reinfection of slum children: relation with the IgE response

“…This concept is based on evidence that polyclonal IgE stimulation can suppress specific IgE responses to individual antigens [12][13][14], and can also inhibit the activity of mast cells via a saturation of their Fee receptors [12][13][14][15][16]. In this respeci, in the present study we found an inverse correlation between total and specific )M\i\-Ascaris IgE, and have previously reported the existence of mast cell saturation in these slum children [13.21], This suppression of allergic reactivity may reduce the pathological consequences of immune reactions against the parasite, or may represent a mechanism of parasite evasion, as has been proposed for IgG4 antibodies thai block anlibody-dcpendenl killing of schistosomula by human eosinophils [5,6], Thus, immunity to helminth infeclion may be a balance beiween ihe stimulation of immunologicai effector functions and the activation of blocking mechanisms. These results have potentially important implications for the control of helminthic infections in the community, in that treatment programmes thai are sustained for a sufficient lime lo permit significant reductions in total igE levels lo occur may be more efTeclive in preventing reinfection than sporadic 'one hit* type anthelmint applications.…”

“…where individuals with the highest levels of IgE antibody against either adult worms or egg antigens were less likely to be reinfected with Schistosoma haematobium after treatment than those with the lowest levels. Also, a negative correlation has been demonstrated between TgE against adult worm antigens of 5, man.soni and reinfection [6].…”

“…The diirerenl helminthiasis are among the most prevalent of chronic infections of humans, and numerous studies have demonstrated thai there is a process of constant reinfection in endemic areas [1,2], One of the most interesting features of the immtme response to these parasites is the produetion of IgE antibodies [3], and there exists considerable evidence that ihe IgE response may participate in the protection against helminthic infection [4][5][6][7]. For example, the allergic-type reactions mediated by the interaction beiween IgE and mast cells may be important accessory mechanisms in helminih expulsion [8].…”

Expression of a Functional FcεRI on Rat Eosinophils and Macrophages

“…Indeed, several immunoepidemiological studies have evidenced a negative correlation between IgE levels and rates of reinfection by the three species of Schistosoma that are pathogen for humans: namely S. mansoni (12,13), S. haematobium (14), and S. japonicum (15). Besides such indirect evidences, a more direct demonstration of the role of IgE in protective immunity was brought both in vitro and in vivo.…”

The evolution of the Th2 immune responses and its relationships with parasitic diseases and allergy

“…Aunque en los vertebrados que no producen IgE los mecanismos inmunológicos que controlan la infestación helmíntica son eficientes (al menos, para evitar que alteren la supervivencia de la especie) y en algunos animales se ha observado que la IgE no determina la resistencia, los estudios en humanos y otras especies de mamíferos sugieren que esta inmunoglobulina participa en los mecanismos de protección (22,(54)(55)(56)(57). Sin embargo, es difícil precisar la magnitud en que la IgE habría mejorado la respuesta inmunitaria antihelmíntica, pues aun la inmunidad estéril (eliminación completa de los parásitos en un animal infectado) no es un fenómeno usual; además, no se ha descartado que en los estudios epidemiológicos mencionados, la IgE específica sea sólo una señal asociada a la activación de la inmunidad de tipo 2, la cual, con otros mecanismos efectores, se encargaría realmente de la defensa.…”