Lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. II. Humoral responses

The filarial-specific humoral responses (IgG1, IgG2, IgG3, IgG4 and IgE) to a Brugia pahangi antigen was assessed in 9 groups of adult individuals from a Wuchereria bancrofti-endemic area in north-east Tanzania. In 5 of the groups, individuals were negative for microfilariae (mf) and circulating filarial antigen (CFA) and had leg lymphoedema of varying severity ranging from early to more advanced grades. A 6th group had mixed grades of lymphoedema and were actively infected with mf and/or CFA. Three groups of asymptomatic individuals with different infection status (mf+CFA+; mf-CFA+; mf-CFA-) were also included. No differences in the antibody levels were observed between the 5 uninfected pathology groups. However, groups with advanced lymphoedema had a significantly higher level of IgG3 as compared to groups with early lymphoedema. A decline in the IgG4/IgE ratios were observed when moving from groups with early to groups with more advanced lymphoedema, which could indicate that increasing levels of IgE relatively to IgG4 are associated with progression of pathology. When all study groups were compared, higher IgG4/IgE ratios were observed in infected groups than in uninfected groups. This could suggest that high levels of IgG4 relative to IgE protect the parasite, whereas the opposite may play a role in parasite killing. When relating IgG4/IgE ratios to levels of gamma interferon (IFN gamma), a clear inverse relationship was observed. Thus, high levels of IFN gamma were found in groups with low IgG4/IgE ratios (uninfected groups) and low levels of IFN gamma were found in groups with high IgG4/IgE ratios (infected groups). The relationship between cellular (IFN gamma) and humoral (IgG4/IgE ratios) responses and their possible role in parasite protection and killing, and in development of early lymphoedema, are discussed.