The relationship between age, sex, egg‐count and specific antibody responses against Schistosoma mansoni antigens in a Ugandan fishing community

Abstract

SummaryIn schistosomiasis endemic areas, antibody isotype responses against Schistosoma mansoni antigens vary with host age, sex and duration or intensity of infection, and are associated with susceptibility or resistance to infection. Identifying the quality and quantity of these responses is important to our understanding of the host-parasite relationship; however, the various host and parasite factors have a strong tendency to confound each other. We investigated the relationships and interactions between age, sex, faecal egg-counts and specific antibody isotype (IgA, IgG1, IgG2, IgG3, IgG4, IgE, IgM) responses to S. mansoni worm (SWA) and egg (SEA) antigens, amongst 380 individuals aged 5-59 from a fishing community from Uganda. This community was characterized by high levels of exposure, and high infection intensities, with higher infection intensities in males than in females. Multivariate anova was conducted with interaction terms between the three categorized explanatory variables. Most anti-SWA responses increased with age, whereas anti-SEA responses tended to decline with age, especially after puberty. IgG1-SWA, IgG4-SWA, IgG4-SEA, IgE-SWA responses increased with egg count, whereas IgG2-SEA decreased with egg count. IgG1-SWA, IgG4-SWA, IgE-SWA and IgG4-SEA responses were independently higher in males, whereas IgG2-SEA responses were independently higher in females. The significant effects of sex on isotype responses to adult worm antigens may be partly because of different levels of cumulative exposure. IgG4-SEA and IgG4-SWA were both strongly correlated with egg count.Patterns of IgE-SWA responses were qualitatively different to IgG4 responses, suggesting independent pathways of regulation.

Increased Human IgE Induced by Killing Schistosoma mansoni In Vivo Is Associated with Pretreatment Th2 Cytokine Responsiveness to Worm Antigens

“…As in this study, most Ab isotype responses against worm Ag, such as SWA, increase with age, whereas SEA responses often decline, or are unchanged. We observed similar relationships between pretreatment SWA Ab levels with age in a neighboring Ugandan fishing community (29), in S. mansoni endemic areas of Kenya (6,23) and Brazil (34), and in S. japonicum endemic areas of the Philippines (13). Generally similar, but not identical, Ab-age patterns, including an age-dependent increase in worm-IgE, have been reported by others (8,35,36).…”

“…The pretreatment age patterns of mean Ab isotype to SEA and SWA ( Fig. 1) were broadly similar to those we had observed in the neighboring community of Piida (29). Generally, the mean responses against SEA declined, particularly IgG2, or were unchanged with age, whereas most SWA Ab isotype responses, particularly SWA-IgG1, -IgG2, -IgG4, and -IgE, increased (Fig.…”

“…Human IgE and IgG1-4, IgA, and IgM responses to S. mansoni SWA, SEA; and IgE, IgG1, and IgG4 responses to rSm22.6 were measured using biotin-labeled isotype specific mAb as described previously (29). Plasma samples were assayed at dilutions of 1/200 for IgG1, IgG4, IgM, and IgA; 1/100 for IgG2 and IgG3; and 1/20 for IgE.…”

Identification of a Novel Antigen ofSchistosoma mansoniShared withPlasmodium falciparumand Evaluation of Different Cross-Reactive Antibody Subclasses Induced by Human Schistosomiasis and Malaria

“…However, in this Ugandan community, there were significant positive correlations between the intensity of S. mansoni infection and IgG4 responses to S. mansoni antigens, including SmLRR, and anti-SmLRR IgG4 responses were strongly positively correlated with anti-Pfs IgG4 responses. The IgG4 response is a major human response to chronic helminthiasis (6,8,14,27) and is often the only IgG subclass response that correlates with the intensity of schistosome (20,24) and other helminth (20) infections. As seen previously, the IgG3 responses to malaria and schistosome antigens, including SmLRR, positively correlated with each other but were not related to the intensity of S. mansoni infection.…”

Carriage of DRB1*13 Is Associated with Increased Posttreatment IgE Levels against Schistosoma mansoni Antigens and Lower Long-Term Reinfection Levels

“…Conversely, IgE levels in response to S. mansoni worm Ags increase with age before treatment (2) and are increased further when measured several weeks after treatment (3,4). These increases in IgE levels after treatment are concomitant with increases in Th2 cytokine responsiveness to worm Ags (5) and have been correlated with resistance to reinfection measured several years after treatment (3).…”