Antigen-driven basophil activation is indicative of early Necator americanus infection in IgE-seronegative patients.
BACKGROUND
Parasitic worms induce a strong, polarized T(H)2-type immune response. The kinetics of gastrointestinal nematode-induced T(H)2-type responses, especially in the context of primary infection, have been extensively studied in experimental infection models but not in human subjects.


OBJECTIVE
We sought to determine the kinetics of basophil sensitization in subjects infected with Necator americanus during the first 12 weeks after infection.


METHODS
Thirty nonasthmatic subjects with allergic rhinoconjunctivitis were randomized in a double-blind manner to cutaneous administration of either 10 hookworm infective larvae or histamine placebo. Blood samples were taken at regular intervals for 12 weeks, and basophil activation was determined in whole blood by measuring CD63 and CD203c levels on stimulation with N americanus excretions/secretions. Parasite-specific immunoglobulin responses were assessed by means of ELISA and Western blotting.


RESULTS
Median values reflecting basophil activation (CD203c/CD63 double-positive cells) in the excretion/secretion-stimulated infected group steadily increased after week 4, consistently achieving statistical significance compared with the placebo group between 6 and 12 weeks after infection. Only parasite-specific IgM levels increased significantly during this period, whereas total and parasite-specific IgE levels did not differ between groups.


CONCLUSIONS
Basophils are sensitized early in the context of a low-dose primary infection with N americanus in the absence of measurable total and specific IgE serum level increase.
School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
Franco H
FH
Falcone
Gary
G
Telford
Doreen
D
Hooi
Alan P
AP
Brown
Rita
R
Seabra
Johanna
J
Feary
Andrea
A
Venn
John
J
Britton
David I
DI
Pritchard
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000947:Antigens, Helminth / Q000276:immunology; D001491:Basophils / Q000276:immunology* / Q000469:parasitology; D004311:Double-Blind Method; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D017221:Necator americanus / Q000276:immunology*; D009332:Necatoriasis / Q000276:immunology* / Q000469:parasitology; D010727:Phosphoric Diester Hydrolases / Q000276:immunology / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D011755:Pyrophosphatases / Q000276:immunology / Q000378:metabolism; D060149:Tetraspanin 30
D000909:Antibodies, Helminth; D015703:Antigens, CD; D000947:Antigens, Helminth; C554586:CD63 protein, human; C427944:ENPP3 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D007073:Immunoglobulin E; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases