Filarial-Specific Antibody Response in East African Bancroftian Filariasis: Effects of Host Infection, Clinical Disease, and Filarial Endemicity

Abstract

The effect of host infection, chronic clinical disease, and transmission intensity on the patterns of specific antibody responses in Bancroftian filariasis was assessed by analyzing specific IgG1, IgG2, IgG3, IgG4, and IgE profiles among adults from two communities with high and low Wuchereria bancrofti endemicity. In the high endemicity community, intensities of the measured antibodies were significantly associated with infection status. IgG1, IgG2, and IgE were negatively associated with microfilaria (MF) status, IgG3 was negatively associated with circulating filarial antigen (CFA) status, and IgG4 was positively associated with CFA status. None of the associations were significantly influenced by chronic lymphatic disease status. In contrast, IgG1, IgG2, and IgG4 responses were less vigorous in the low endemicity community and, except for IgG4, did not show any significant associations with MF or CFA status. The IgG3 responses were considerably more vigorous in the low endemicity community than in the high endemicity one. Only IgG4 responses exhibited a rather similar pattern in the two communities, being significantly positively associated with CFA status in both communities. The IgG4:IgE ratios were higher in infection-positive individuals than in infection-negative ones, and higher in the high endemicity community than in the low endemicity one. Overall, these results indicate that specific antibody responses in Bancroftian filariasis are more related to infection status than to chronic lymphatic disease status. They also suggest that community transmission intensity play a dominant but subtle role in shaping the observed response patterns.

Immunoepidemiology ofWuchereria bancroftiInfection: Parasite Transmission Intensity, Filaria-Specific Antibodies, and Host Immunity in Two East African Communities

“…In contrast to the specific IgG1, IgG2, and IgE responses, the mean levels of IgG4 in both communities increased with age, and the rate of increase was higher in the high-transmission community. This finding clearly mirrors previous observations (12,20) and is perhaps not surprising since IgG4 levels are generally thought to be positively associated with the presence and intensity of infection (4,13,19,29,42). The converse age response patterns for specific IgG4 and IgE appear to also underlie the finding in this study that the mean IgG4/IgE intensity ratio varied positively with both transmission intensity and increasing host age, an observation contrary to previous suggestions that in lymphatic filariasis this ratio may be a measure of the strength of immunological resistance to infection and hence expected to be low in the presence of resistance and vice versa (18).…”

“…The results describing the individual or univariate associations between infection intensity and W. bancrofti-specific antibody levels in relation to the ages of individuals from the two study communities, based on the age-stratified Pearson product moment partial correlation test, are shown in Tables 3 and 4. This test determines the correlation between host infection intensity and a specific antibody level after any joint effects due to the responses of the other antibody isotypes examined are controlled for (13). Hence, it essentially examines the independent effects of each antibody in regulating parasite infection intensity.…”

“…The reasons for this striking inverse relationship with exposure intensity and the observed between-community impact of this isotype is not clear, but the data suggest either that the effects of this antibody are manifest only at lower levels coupled with a complex down-regulatory role for exposure intensity under high-transmission conditions or that this finding is an artifact of closely linked changes in some other effective component of the immune response. Further studies, perhaps specifically focusing on specific IgG3 responses in parallel with cellular components known to be associated with the IgG3 response (7) in communities with very different transmission intensities, are warranted if we are to successfully dissect the role of IgG3 in regulating filariasis infection (13). In contrast to the specific IgG1, IgG2, and IgE responses, the mean levels of IgG4 in both communities increased with age, and the rate of increase was higher in the high-transmission community.…”

“…The primary design involved collection of samples and data for determining individual host infection and antibody levels in order to quantify, model, and compare age copatterns of these variables between the two communities. Individuals from both communities were also examined for chronic clinical status; however, the outcomes were not taken into account in the present analyses because of our previous finding that disease manifestations did not significantly affect antifilaria antibody responses (13). A detailed description of the study communities has been given elsewhere (43), together with findings from clinical, microfilaria (mf), and circulating filarial antigen (CFA) examinations.…”

“…Sera were examined for the presence of filaria-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgE antibodies with an enzyme-linked immunosorbent assay. The methods used for preparation of antigen from Brugia pahangi adult worms recovered from experimentally infected jirds (Meriones unguiculatus) and for conducting the specific antibody assays have been described in detail previously (13).…”