A major allergen of lymphatic filarial nematodes is a parasite homolog of the gamma-glutamyl transpeptidase.
BACKGROUND
Bm2325, a major IgE-inducing antigen of the filarial parasite Brugia malayi has been implicated in the pathology of tropical pulmonary eosinophilia (TPE), a pulmonary syndrome thought to result from hypersensitivity to microfilariae.


METHODS
Affinity-purified IgE to Bm2325 from patients with TPE was used to identify a complementary DNA (cDNA) from a B. malayi expression library. Sequence analysis of the cDNA revealed a hitherto unknown parasite protein. Immunoblotting of the recombinant filarial protein using sera of patients with TPE determined its IgE-binding capacity. Reactivity to human lung epithelial cell proteins was analyzed using murine anti-Bm2325 antibodies and serum from patients with TPE.


RESULTS
The predicted protein is a homolog of the entire precursor of the gamma-glutamyl transpeptidase (gamma-GT), a key enzyme in the synthesis and degradation of glutathione. The filarial precursor encodes both the heavy (H) and the light (L) chain subunits and shares structural similarities with the mammalian enzymes. The Bm2325 allergen was identified as the homolog of the enzyme light chain subunit. Murine antibodies against the recombinant parasite gamma-GT cross-reacted with the human enzyme present in human airway epithelial cells, and human gamma-GT is a target of antibodies present in the serum of patients with TPE.


CONCLUSIONS
Molecular mimicry between the parasite gamma-GT homolog and the host membrane-bound gamma-GT present in lung epithelial cells likely contributes to the pathogenesis observed in tropical pulmonary eosinophilia.
Lobos
E
E
Department of Medical Parasitology, Swiss Tropical Institute, Basel, Switzerland.
Zahn
R
R
Weiss
N
N
Nutman
T B
TB
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D017178:Brugia malayi / Q000276:immunology*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004605:Elephantiasis, Filarial / Q000469:parasitology*; D004802:Eosinophilia / Q000469:parasitology* / Q000503:physiopathology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D017385:Sequence Homology; D005723:gamma-Glutamyltransferase / Q000737:chemistry* / Q000378:metabolism
D000947:Antigens, Helminth; D001323:Autoantibodies; D017931:DNA Primers; D008565:Membrane Proteins; D007073:Immunoglobulin E; D005723:gamma-Glutamyltransferase