Factors affecting human IgE and IgG responses to allergen-like Schistosoma mansoni antigens: Molecular structure and patterns of in vivo exposure.
BACKGROUND
The human IgE response is associated with allergy and with host defence against parasitic worms. A response to Sm22.6, the dominant IgE antigen in adult Schistosoma mansoni worms, correlates with resistance to re-infection after treatment. Sm22.6 is one of a family of EF-hand containing parasite proteins with sequence similarity to dynein light chain (DLC) and with major non-parasite allergens. Here we compare human IgE and IgG responses to other family members, Sm20.8 and Sm21.7, as well as to SmDLC1, relating these to antigen structure and expression in parasite life stages.


METHODS
Recombinant antigens were used in ELISA to measure antibody isotype responses in 177 cases from an endemic area, before and 7 weeks after treatment. Parasite antigen expression was assessed by RT-PCR and Western blotting.


RESULTS
Levels of antibodies to Sm22.6 and Sm20.8 (but not to Sm21.7 or SmDLC1) showed posttreatment increases in all but young children. Many produced IgE to Sm22.6 and Sm20.8 (2 EF-hands), few to Sm21.7 (1 EF-hand) or SmDLC1 (no EF-hands). Sm21.7 was expressed in cercariae, adults and eggs, Sm22.6 and Sm20.8 were concentrated in the adult.


CONCLUSIONS
These studies suggest that IgE antigens Sm22.6 and Sm20.8 are only released to boost antibodies when adult worms die, whilst Sm21.7 and SmDLC1 are released constantly from eggs dying in host tissue. IgE responses to these allergen-like molecules may be influenced by patterns of exposure and the number of EF-hand motifs.
Fitzsimmons
Colin M
CM
Department of Pathology, University of Cambridge, Cambridge, UK. cmf1000@cam.ac.uk
McBeath
Rowena
R
Joseph
Sarah
S
Jones
Frances M
FM
Walter
Klaudia
K
Hoffmann
Karl F
KF
Kariuki
H Curtis
HC
Mwatha
Joseph K
JK
Kimani
Guchuhi
G
Kabatereine
Narcis B
NB
Vennervald
Birgitte J
BJ
Ouma
John H
JH
Dunne
David W
DW
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002648:Child; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D011223:Praziquantel / Q000627:therapeutic use; D012333:RNA, Messenger / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology*; D014454:Uganda
D000485:Allergens; D000871:Anthelmintics; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007074:Immunoglobulin G; D012333:RNA, Messenger; D007073:Immunoglobulin E; D011223:Praziquantel