Development of Antibody Isotype Responses toSchistosoma mansoniin an Immunologically Naive Immigrant Population: Influence of Infection Duration, Infection Intensity, and Host Age

Abstract

We have identified the influence of host and parasite factors that give rise to characteristic antibody isotype profiles with age seen in human populations living in different areas of schistosomiasis endemicity. This is important in the immunobiology of this disease. It is also of interest in the context of human responses to chronic antigen stimulation, vaccines, allergens, and other pathogens. In populations exposed to endemic schistosomiasis, factors such as intensity and duration of infection are age dependent. They therefore confound the influence of host age on antiparasite responses. Here, we resolved these confounding factors by comparing the developing antibody responses of an immunologically naive immigrant population as they acquired the infection for the first time with those of chronically infected resident inhabitants of the same region of Schistosoma mansoni endemicity in Kenya. Recent arrival in the area strongly favored immunoglobulin G3 (IgG3) responses against the parasite. The antibody isotype responses associated with human susceptibility to reinfection after chemotherapy were elevated in those suffering high intensities of infection (IgG4 responses against worm and egg antigens) or were characteristic responses of young children irrespective of the intensity or duration of infection (IgG2 responses against egg antigen). IgE responses against the adult worm, a response associated with resistance to reinfection after chemotherapy, increased with the ages of infected individuals and were also favored in those currently suffering higher intensities of infection.

Associations between specific antibody responses and resistance to reinfection in a Senegalese population recently exposed to Schistosoma mansoni

“…This study confirms the results of previous studies on specific antibody responses in recently exposed communities by demonstrating that age, and/or intensity of infection and/or experience of infection influence specific antibody isotype responses against schistosome antigens, depending on the isotype Naus et al 1999). In addition, we demonstrated that treatment and subsequent re-exposure and reinfection affect anti-schistosome antibody responses and that the effect of treatment on the humoral immune response is influenced by age, intensity of infection and duration of exposure.…”

“…As observed previously, IgG1 and IgG4 responses to SWA as well as IgG4-SEA showed a similar age profile as levels of intensity of infection, while IgE and IgA responses to SWA and SEA increased with age and SWA-and SEA-specific IgM responses were more or less similar in adults and children Ndhlovu et al 1996;Webster et al 1997;Naus et al 1999Naus et al , 2003). In contrast to previous studies on populations that were recently and chronically exposed to S. mansoni, IgG2 and IgG3 responses against SWA and SEA tended to increased with age (Webster et al 1997;Naus et al 1999Naus et al , 2003. On the other hand, our results were in concordance with those of van in a recent focus in Senegal.…”

“…Specific IgG1, IgG2, IgG3, IgG4, IgE, IgA and IgM responses to S. mansoni soluble worm antigen (SWA) and soluble egg antigen (SEA) were measured b.y enzyme-linked immunoassay technique (ELISA) using methods similar to those described previously (Naus et al 1999). Both antigen preparations were purchased from Prof. A. Deelder (LUMC, Leiden, The Netherlands).…”

“…However, the underlying epidemiology of the humoral immune response against schistosomiasis is quite complicated. Infected individuals of all ages have high levels of circulating antibodies with anti-schistosome specificity and the class and subclass composition of these antibodies vary with age, sex and intensity of infection Mutapi et al 1997;Webster et al 1997;Naus et al 1999Naus et al , 2003. The class and subclass distribution of the antibody response is instrumental because each isotype has a specific biological function (Spiegelberg 1989).…”

Spatial awareness in parasite immuno‐epidemiology

“…A recent example of where both age and sex were important factors in affecting the relationship between immune responses and disease was observed in a study of Schistosoma mansoni infection in a fishing community in Uganda (11). Duration of residency in an area where infections are endemic has been implicated not only in the development of antibody response profiles (12), but also in the risk of presenting with periportal fibrosis by a given age (13).…”