Noninflammatory gluten peptide analogs as biomarkers for celiac sprue.
New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for noninvasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized noninflammatory gluten peptide analogs in which key Gln residues are replaced by Asn or His. Like their proinflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2, or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.
Bethune
Michael T
MT
Department of Biochemistry, Stanford University, CA 94305, USA.
Crespo-Bosque
Mónica
M
Bergseng
Elin
E
Mazumdar
Kaushiki
K
Doyle
Lara
L
Sestak
Karol
K
Sollid
Ludvig M
LM
Khosla
Chaitan
C
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism*; D005983:Glutens / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D010455:Peptides; D005983:Glutens; D011503:Transglutaminases