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Infection and Immunity, February 2003, p. 747-753, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.747-753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Elevated Immunoglobulin E against Recombinant Brugia malayi {gamma}-Glutamyl Transpeptidase in Patients with Bancroftian Filariasis: Association with Tropical Pulmonary Eosinophilia or Putative Immunity

Edgar Lobos,1* Thomas B. Nutman,2 John S. Hothersall,3 and Salvador Moncada1

The Wolfson Institute for Biomedical Research,1 Institute of Urology and Nephrology,3 University College London, London, United Kingdom, and Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland2

Received 16 July 2002/ Returned for modification 15 September 2002/ Accepted 30 October 2002

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.

* Corresponding author. Present address: Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103 Leipzig, Germany. Phone: 49-341-97-22051. Fax: 49-341-97-22009. E-mail: lobe{at}medizin.uni-leipzig.de.

Editor: W. A. Petri, Jr.

Infection and Immunity, February 2003, p. 747-753, Vol. 71, No. 2
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.2.747-753.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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