Antibody isotype responses to Schistosoma japonicum antigens in subjects from a schistosomiasis area with repeated praziquantel chemotherapy compared with a new endemic zone in Hunan Province, P.R. China

Abstract

To demonstrate the dynamics of specific antibody isotypes against schistosome adult worm (AWA) and soluble egg (SEA) antigens, we evaluated (in 1999-2000) 112 subjects infected with Schistosoma japonicum from 2 regions of Hunan Province, China. Fifty-eight subjects were from Area A, a well-known endemic area with repeated chemotherapy. Area B (n = 54) is a new endemic focus in another part of the same province. Serum samples were collected prior to praziquantel (PZQ) chemotherapy, and at 2 and 12 months post-treatment. IgM, IgA, IgG, IgG2, IgG4 and IgE antibodies to AWA and SEA were measured by quantitative enzyme-linked immunosorbent assay (ELISA). Pre-treatment antibody isotype levels from Area A, except IgA against AWA and SEA, were significantly higher than those from Area B. In response to chemotherapy, most antibody isotype levels fell or remained stable. However, in Area A there was a significant increase in the IgA, IgE and IgG4 responses to AWA 2 months after PZQ--which fell to approach pre-treatment levels by 12 months. A similar response was seen in Area B with IgE and IgG4 to AWA. Levels of all AWA-specific IgE and IgG4 were significantly higher in subjects from Area A compared with Area B at all time-points. AWA-IgE levels demonstrated significant linear correlations with age and number of previous PZQ treatments in Area A only. All SEA-specific isotypes in both areas fell significantly in response to treatment--except IgE, which remained stable in both area. All SEA-specific isotype levels (except IgA) were significantly higher from Area A at baseline. This significant difference was maintained through 12-months follow-up for IgE, IgG2 and IgG4 only. This study suggests that multiple episodes of schistosome infection may be required to generate antibody isotype levels that have been associated with resistance to re-infection in other studies. Further, a surrogate marker of successful chemotherapy (AWA-IgG4) performed less effectively in patients with previous treatment courses.

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

“…In the endemic area, worm-IgE and -IgG4 increased by 8 wk posttreatment and were significantly correlated with age and number of previous treatments. Worm-Abs also increased in the new focus, but worm-IgE was lower at all time points (44). Both these studies suggest that multiple episodes of infection and worm death may be required to generate the elevated worm-IgE associated with reinfection resistance.…”

Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

“…An interesting finding was a negative standardized mean difference observed in the association between IgE levels and reinfection with schistosomes (Figure 5 and Figure S2) inferred from meta-analysis on 8 studies [23], [31], [39], [44], [48]–[51]. However, subgroup analyses of these associations with IgE levels against adult worm antigen (SWA) (Figure 5A) and egg antigen (SEA) (Figure 5B) were not statistically significant (For anti-SWA IgE, SMD = −0.06, 95% CI = −0.59–0.46, Z = 0.23, p  = 0.82; for anti-SEA IgE, SMD = −0.03, 95% CI = −0.38–0.32, Z = 0.15, p  = 0.88).…”

“…Finally, 32 study reports on 26 host determinants of reinfection were included in the final quantitative data synthesis (meta-analysis). Five of these study reports were on two independent data sets [23]–[27], thus, a total of 37 datasets were included in the meta-analysis (Figure 1). …”

Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target

“…Human sera from confirmed schistosomiasis japonica cases (n = 72) by microscopy with fecal egg identification and serology against adult worm antigens before treatment [15] were collected from Han Chinese patients from endemic areas of Hunan province, People's Republic of China (PRC) and 24 normal sera were collected from healthy Han Chinese from Xinjiang, PRC, where schistosomiasis is not endemic. The human sera were diluted 1 in 100 with SMPT.…”