A major
allergen of the lymphatic filarial nematode Brugia malayi, a homologue of
gamma-glutamyl transpeptidase (gamma-GT), is involved in the pathology of tropical
pulmonary eosinophilia (TPE) through its potent allergenicity and the induction of
antibodies against the host pulmonary epithelium. To investigate the
immunoglobulin G (
IgG) subclass and
IgE responses to recombinant B. malayi gamma-GT, we analyzed the results obtained from 51 patients with differing clinical manifestations of
bancroftian filariasis. gamma-GT-specific
IgG1, rather than
IgG4, was the predominant
IgG subclass, particularly in patients with TPE (geomean, 6,321 ng/ml; range, 78 to 354,867 ng/ml) and was 75 times higher than in patients with
elephantiasis (CP) (P < 0.003) and 185 times higher than in endemic normal individuals (ENL) (P < 0.010).
IgG2 responses were low and
IgG3 was almost absent, with no significant differences among the groups. gamma-GT-specific
IgG4 responses were significantly elevated in those with subclinical microfilaremia (MF) compared to the CP and ENL groups and correlated with the presence of circulating filarial
antigen (CAg). More significantly, gamma-GT-specific
IgE antibody levels were strikingly elevated in patients with TPE (geomean, 681 ng/ml; range, 61 to 23,841 ng/ml) and in the ENL group (geomean, 106 ng/ml; range, 13 to 1,405 ng/ml) whereas the gamma-GT-specific
IgE level was 44 and 61 times lower in those with MF and CP, respectively (P < 0.001). Elevated gamma-GT-specific
IgE/
IgG4 ratios were demonstrated in patients with TPE (ratio, 45) and ENL (ratio, 107). Because expression of gamma-GT in Brugia infective third-stage larvae (L3) was demonstrated by immunoblot analysis, the elevated gamma-GT-specific
IgE antibodies appear to be associated not only with pulmonary pathology but also with possible resistance to
infection in
lymphatic filariasis.