Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.

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Chicken egg yolk immunoglobulin Y (IgY) is a promising alternative for the prevention of enteric gliadin absorption, the predisposing factor of celiac disease (CD). IgY antibody was produced from the egg yolk of Single Comb White Leghorn chickens during the immunization period for the development of an oral immunotherapeutic agent. Here, we report the potential use of spray dried IgY antibody formulation using sugar protectants (mannitol, sorbitol, or microcrystalline cellulose powder (MCCP)). The long-term stability of the spray dried egg yolk powder formulated with 37.5% mannitol (EYP-M) preserved IgY antibody activity at 99.9%, which was significantly higher than that with other protectants (p < 0.05). In a dissolution test, the EYP-M shows 82.4% IgY activity after 2 h in simulated gastric fluid (SGF). A competitive ELISA at 50% inhibition (IC(50)) shows that 1.6 mg/mL EYP-M bound to 7.6 mg/mL and 10.5 mg/mL gliadin in SGF without and with food matrix conditions, respectively, whereas in simulated intestinal fluid, the formulation bound to 10 mg/mL gliadin, regardless of a food matrix. In-vivo study: BALB/c mice fed with EYP-M and gliadin at a ratio of 1:5 (w/w) demonstrated that gliadin absorption in the gastrointestinal tract was minimal at <1%. Thus, EYP-M containing IgY antibody may be used in CD patients to eliminate the effects of ingested toxic gliadin.

BackgroundPepsin-trypsin resistant gliadin (PT-gliadin) promotes intestinal tissue inflammation and increases paracellular permeability of immunogenic gliadin peptides into the lamina propria. This leads to the complications seen in the pathogenesis of celiac disease (CD). In this study, specific anti-gliadin IgY antibody was produced and evaluated for its efficacy on gliadin induced intestinal integrity impairment and proinflammatory effects on intestinal epithelial (Caco-2) cell culture model for CD.MethodsCaco-2 (passages 20-24) monolayers were subjected to 7 experimental conditions (n=3 each): phosphatebufferedsaline (PBS; control), pancreatic digested-casein (PD-casein; negative control), PT-gliadin (positive control), non-specific IgY with PT-gliadin, and anti-wheat gliadin IgY with PT-gliadin at a ratio of 1:6,000, 1:3,000 and 1:1,500. Caco-2 monolayers were then evaluated for effects of gliadin and/or anti-wheat gliadin IgY after 24 h exposure. Enzyme-linked immunosorbent assay (ELISA) was used to quantify anti-inflammatory markers (TNF-α and IL-1β) 5 days after cells were exposed to PT-gliadin and/or anti-wheat gliadin IgY.ResultsAmong other conditions, anti-wheat gliadin IgY at a ratio of 1:3,000 (anti-gliadin IgY: PT-gliadin) significantlyprevented gliadin toxicity on Caco-2 by maintaining intestinal integrity, inhibiting phenol red permeation, and inhibiting gliadin absorption and production of proinflammatory cytokines (TNF-α and IL-1β) as compared to PT-gliadin stimulated cultures (P < 0.05).ConclusionThe anti-wheat gliadin IgY antibody produced in this study has proved to inhibit absorption of gliadin and gliadin-induced inflammatory response in Caco2 cell culture model of CD. Anti-gliadin IgY, therefore has potential to be used as an oral passive antibody therapy to treat CD.

In our cohort, AGY was safe and potentially associated with improved CD-related outcome measures in patients on a GFD. A larger study powered for further safety and efficacy evaluation is planned.