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. 2022 May 26:3:900573.
doi: 10.3389/falgy.2022.900573. eCollection 2022.

Development of a Sequence Searchable Database of Celiac Disease-Associated Peptides and Proteins for Risk Assessment of Novel Food Proteins

Plaimein Amnuaycheewa  1 , Mohamed Abdelmoteleb  2 , John Wise  3 , Barbara Bohle  4 , Fatima Ferreira  5 , Afua O Tetteh  6 , Steve L Taylor  3 , Richard E Goodman  3
Affiliations

Development of a Sequence Searchable Database of Celiac Disease-Associated Peptides and Proteins for Risk Assessment of Novel Food Proteins

Plaimein Amnuaycheewa et al. Front Allergy. .

Abstract

Celiac disease (CeD) is an autoimmune enteropathy induced by prolamin and glutelin proteins in wheat, barley, rye, and triticale recognized by genetically restricted major histocompatibility (MHC) receptors. Patients with CeD must avoid consuming these proteins. Regulators in Europe and the United States expect an evaluation of CeD risks from proteins in genetically modified (GM) crops or novel foods for wheat-related proteins. Our database includes evidence-based causative peptides and proteins and two amino acid sequence comparison tools for CeD risk assessment. Sequence entries are based on the review of published studies of specific gluten-reactive T cell activation or intestinal epithelial toxicity. The initial database in 2012 was updated in 2018 and 2022. The current database holds 1,041 causative peptides and 76 representative proteins. The FASTA sequence comparison of 76 representative CeD proteins provides an insurance for possible unreported epitopes. Validation was conducted using protein homologs from Pooideae and non-Pooideae monocots, dicots, and non-plant proteins. Criteria for minimum percent identity and maximum E-scores are guidelines. Exact matches to any of the 1,041 peptides suggest risks, while FASTA alignment to the 76 CeD proteins suggests possible risks. Matched proteins should be tested further by CeD-specific CD4/8+ T cell assays or in vivo challenges before their use in foods.

Keywords: Pooideae; T-cell epitopes; celiac disease; gluten; peptide database; prolamin; risk assessment; sequence comparison.

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Conflict of interest statement

RG declares limited funding from six biotechnology companies from 2009 to 2012 for support of the database management. Unilever SEAC and NuSeed Americas provided limited funding to the AllergenOnline.org database from 2018 to 2021. These companies did not contribute to or see the article prior to submission. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Taxonomic tree of cereal and dicotyledonous plants based on NCBI taxonomy. Published evidence of CeD safe foods show reactions only to grains of the Pooideae subfamily of grasses.
Figure 2
Figure 2
(A) Amino acid sequence alignments of an α-gliadin (NCBI accession number: CAB76964) with 53 overlapping CeD-associated peptides identified with the exact sequence match tool; (B) full FASTA sequence alignment results with homology scores of the α-gliadin theoretically substituted with 13 alanine residues; (C) full FASTA sequence alignment results with homology scores of the α-gliadin theoretically substituted with 11 alanine residues.
Figure 3
Figure 3
Proposed evaluation criteria to predict the likelihood of a query protein to cause elicitation of CeD. An exact match to any of the 1,041 peptides indicates probable rejection. Alternatively, a FASTA3 alignment with an E-score limit of 1e-14 and minimum alignment length > 100 AA with an identity percent of the protein at 45% should trigger testing or rejection.
See this image and copyright information in PMC

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