The effects of ALV003 pre-digestion of gluten on immune response and symptoms in celiac disease in vivo.
Effective treatment of celiac disease is an unmet medical need. A glutenase that destroys immunogenic gluten peptides may be clinically valuable. Twenty patients with celiac disease were randomly assigned to ingest a large gluten meal (16 g daily for 3 days) pre-treated with ALV003, a mixture of highly specific glutenases (n=10), or pre-treated with placebo (n=10). Peripheral blood T-cell IFN-gamma ELISpot responses to gliadin and an immunogenic 33mer and symptoms were assessed. While baseline IFN-gamma ELISpot responses to gliadin and the 33mer were negative in all patients, a significant ELISpot response to gliadin or the 33mer was observed in 6 of 10 patients consuming placebo-treated gluten and 0 of 10 consuming ALV003 pre-treated gluten (p=0.011). Symptoms typically associated with gluten ingestion occurred in both groups and were not significantly reduced by ALV003 pre-treatment. ALV003 pre-treatment can abolish immune responses induced by gluten in patients with celiac disease.
Tye-Din
Jason A
JA
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. tyedin@wehi.edu.au
Anderson
Robert P
RP
Ffrench
Rosemary A
RA
Brown
Gregor J
GJ
Hodsman
Peter
P
Siegel
Matthew
M
Botwick
Wendy
W
Shreeniwas
Revati
R
D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D004311:Double-Blind Method; D010450:Endopeptidases / Q000008:administration & dosage* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D005983:Glutens; D007371:Interferon-gamma; D005903:Gliadin; D010450:Endopeptidases