Maize Prolamins Resistant to Peptic-tryptic Digestion Maintain Immune-recognition by IgA from Some Celiac Disease Patients
Dipartimento di Scienze Molecolari Agroalimentari, Università degli Studi di Milano, Milano, Italy.Plant Foods for Human Nutrition (Impact Factor: 1.98). 02/2012; 67(1):24, 30. DOI: 10.1007/s11130-012-0274-4
Maize is used as an alternative to wheat to elaborate food stuffs for celiac patients in a gluten-free diet.However, some maize prolamins (zeins) contain amino acid sequences that resemble the wheat gluten immunodominant peptides and their integrity after gastrointestinal proteolysisis unknown. In this study, the celiac IgA-immunoreactivity to zeins from raw or nixtamalized grains, before and after peptic/tryptic digestion was evaluated and their possible immunogenicity was investigated by in silico methods.IgA from some celiac patients with HLA-DQ2 or DQ8 haplotypes recognized two alpha-zeins even after peptic/ tryptic proteolysis. However, digestion affected zeins after denaturation, reduction, and alkylation, used for identification of prolamins as alpha-zein A20 and A30 by MS/MS sequencing. An in silico analysis indicated that other zeins contain similar sequences, or sequences that may bind even better to the HLA-DQ2/DQ8 molecules compared to the already identified ones. Results concur to indicate that relative abundance of these zeins, along with factors affecting their resistance to proteolysis, may be of paramount clinical relevance, and the use of maize in the formulation and preparation of gluten-free foods must be reevaluated in some cases of celiac disease.
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- "Da) (Shan et al., 2002), α-zein 34-mer (LQQAIAASNIPLSPLLFQQSPALSLVQSLVQTIR; MW = 3646.32 Da) (Cabrera-Chávez et al., 2012), and the toxic peptide α-gliadin p31–49 (LGQQQPFPPQQPYPQPQPF; MW = 2222.51 Da) (Maiuri et al., 2003; Matysiak-Budnik et al., 2003), were supplied by United Biosystems (USA) with purities of 97.54%, 95.66% and 95.18%, respectively. "
ABSTRACT: We study the effect of maize zeins on cellular immune response as compared to that of wheat gliadins for exacerbating celiac disease due to a hypothetical similar response in some patients. In vitro activation of celiac duodenal mucosa with gliadin or zein immunoreactive peptides and pro-inflammatory response of CACO-2 cells to digested gliadin or zein fractions were evaluated as indicators of adaptive and innate response, respectively. In 3/5 biopsies, zein increased production of IFN-γ, whereas gliadin has done it in all the patient biopsies. In CACO-2 cells, two zein fractions (3–5 and 1–3 kDa), similar to gliadin fractions, stimulated the production of IL-8, p38 MAPK, COX2, and release of ZO-1 as compared to medium alone. The 3–5 kDa zein fraction increased permeability in cell monolayers, although less than gliadin. Zein peptides are immunogenic for some patients and induce a similar innate response, but to a lesser extent than gliadin peptides.
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ABSTRACT: Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet.
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ABSTRACT: A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease, an autoimmune disorder of the small intestine associated with a permanent intolerance to gluten proteins. The complete elimination of gluten proteins contained in cereals from the diet is the key to celiac disease management. However, this generates numerous social and economic repercussions due to the ubiquity of gluten in foods. The research presented in this review focuses on the current status of alternative cereals and pseudocereals and their derivatives obtained by natural selection, breeding programs and transgenic or enzymatic technology, potential tolerated by celiac people. Finally, we describe several strategies for detoxification of dietary gluten. These included enzymatic cleavage of gliadin fragment by Prolyl endopeptidases (PEPs) from different organisms, degradation of toxic peptides by germinating cereal enzymes and transamidation of cereal flours. This information can be used to search for and develop cereals with the baking and nutritional qualities of toxic cereals, but which do not exacerbate this condition.
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