Celiac or Coeliac disease is an inherited autoimmune disorder that triggers a negative response following gluten ingestion. Despite few similarities in gastrointestinal manifestations, celiac disease should not be confused with wheat allergy which is an immune (different from autoimmune) disorder characterized by the production of specific immunoglobulin E (IgE).

Celiac disease occurs in persons who:^1,2

• Are genetically predisposed (carry either HLA-DQ2 and/or HLA-DQ8 alleles).
• Consume gluten, a storage protein found in wheat, barley, and rye, and their hybridized strains.
• Are susceptible to disease activation triggers mainly stress, trauma, viral infections, and other environmental factors.

Although 33% of the general population has the genetic predisposition for celiac disease, only 0.5-1.0% will develop the condition.³ In the US, celiac disease is 4 to 8 times more prevalent in Caucasians compared to other races.⁴

Proteins known to trigger celiac disease include prolamin-containing gluten fractions, glutenin and gliadin found in gluten from wheat, rye, and barley. Grains such as corn, rice, sorghum, and millet do not contain celiac-active prolamins, thus are not involved in celiac disease development. Oats are unique in that they contain very low amounts of avenin, a prolamin-type protein, thus are not expected to trigger celiac disease symptoms. However, oats are often contaminated with gluten from other cereals. Therefore, celiac patients are strongly advised to exclude oats from their diet, or choose oats that have the gluten-free seal.⁵

Mechanism and onset of celiac disease flare ups

Following the ingestion of gluten-containing foods, celiac patients undergo a series of autoimmune responses which lead ultimately to gastrointestinal problems and ultimately resulting in severely damaging the intestinal lining. Celiac disease onset takes place via two phases:

• Phase 1: involves the development of specific antibodies and intestinal mucosal legions (enteropathy) which can cause nutrients’ malabsorption.⁶
• Phase 2: involves the release of autoantigens via tissue transglutaminase activity and deamidation or cross-linking of gluten peptides resulting in T-cell activation, cytokine production, mucosal inflammation, and destruction of intestinal lining.⁷

Symptoms and Clinical Manifestations

Celiac disease is characterized by a wide range of symptoms and clinical presentations in all age groups. Over 200 symptoms have been recorded in celiac sufferers. Common signs of celiac disease that are directly related to the body’s inability to properly digest food include:

• Diarrhea, bloating and gas, vomiting, mouth ulcers, fatigue, etc.
• Less severe symptoms such as malabsorption and subsequent weight loss.

Other signs that may not be directly related to the digestive system including:

• Impaired weight or height gain, or delayed puberty in children.
• Infertility, osteoporosis, iron deficiency or other deficiency syndromes in adults.
• Dermatitis herpetiformis that manifests as a skin rash and affects approximately 10-15% of celiac patients.

Diagnosis of celiac disease^8,9

In addition to gastrointestinal indications, confirmation of the occurrence of celiac disease relies on a combination of essential diagnostic tests, mainly:

• Blood screening to confirm the presence of autoantibodies against endomysium tissue transglutaminase and deamidated gliadin peptides. For this test, the gastroenterologist requires the patient to consume a gluten-containing diet while closely monitoring symptoms.
• Following a positive blood screening, a small intestinal biopsy is done to confirm the presence of enteropathy which responds to a gluten-free diet.
• In the absence of symptoms, celiac disease can be associated with other autoimmune diseases, with type-1 diabetes mellitus and with IgA deficiency.

Can food processing reduce gluten’s negative impact on celiac patients?

Unfortunately, food processing does not seem to have a positive impact on gluten toxicity for celiac sufferers. Partial hydrolysis and enzymatic peptic-tryptic degradation of gluten do not affect celiac-triggering properties since the important peptide units are unaffected. Similarly, heat treatment (baking, cooking, etc.) does not change celiac toxicity either.

The challenge with celiac disease is that it is a life-long systemic disorder and has no cure so far. In many individuals, celiac disease is often under- or un-diagnosed due to the wide range of clinical manifestations. Early diagnosis and receiving proper medical attention and adhering to gluten-free diets can help individuals enjoy a normal life.

A glimmer of hope for celiac patients

Recent research may finally offer celiac sufferers some hope. The research study reported on the discovery of an enzyme, a peptidase, in the culture medium of Burkholderia gladioli strain that may be effective in digesting immunogenic peptides. The authors proposed that this peptidase may be administered as a potential oral enzyme therapy to help ameliorate the health challenges of celiacs and other gluten-related sufferers. Usefulness of this research was demonstrated in the possibility of making gluten-free beer.¹⁰

References

1. Salazar, C., Garcia-Cardenas, J.M., and Paz-y-Mino, C. understanding celiac disease from genetics to the future diagnostic strategies. Clin. Med. Insights: gastroenterology, 10, pp: 1-13.
2. Sollid, L.M., Markussen, G., Gjerde, H., Vartdal, F., and Throbsy, E. evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J. Exp. Med. 169, pp: 345-350
3. EFSA Panel on Dietetic Products. Scientific opinion on the evaluation of allergenic foods and food ingredients for labelling purposes. 2014, www.efsa.europa.eu/efsajournal.
4. Singh, P., Arora, A., Leffler, D.A., Catassi, C., Green, P.H., Kelly, C.P., Ahuja, V., and Makharia, G.K. Global prevalence of celiac disease: Systematic review and meta-analysis. 2018. Clin. Gastroenterol. Hepatol. 16, 823–836.e2
5.  De Souza, M.C., Deschenes, M.-E., Laurencelle, S., Godet, P., Roy, C.C. and Djilali-Saiah, I. Pure oats as part of the Canadian gluten-free diet in celiac disease: the need to revisit the issue. 2016, Can. J. Gastroenterol. Hepatol. Published online,  doi: 10.1155/2016/1576360.
6.  Ludvigsson, J.F., Leffler, D.A., Bai, J.C., Biagi, F., Fasano, A., Green, P.H., Hadjivassiliou, M., Kaikinen, K., Kelly, C.P., Leonard, J.N., Lundin, K.E., Murray, J.A., Sanders, D.S., Walker, M.M., Zingone, F. and Giacci, C. The Oslo definitions for coeliac disease and related terms. 2013, Gut, 62, pp: 43-52.
7.  Schuppan, D., Junker, Y. and Barisani, D. Celiac disease: from pathogenesis to novel therapies. 2009, Gastroenterology, 137, pp: 1912-1933.
8. Volta, U., and Villanacci, V. Celiac disease: diagnostic criteria in progress. 2011, Cell Mol Immunol, 8, pp: 96-102.
9. Husby, S., Koletzko, S., Korponay-Szabo, I.R., Mearin, M.L., Phillips, A., Shamir, R., Troncone, R., Giersiepen, K., Branski, D., Catassi, C., Lelgeman, M., Maki, M., Ribes-Koninckx, C., Ventura, A., Zimmer, K.P. Guidelines for the diagnosis of coeliac disease. 2012, J. Pediatr. Gastroenterol. Nutr.,54, pp: 136-160.
10. Liu, Y.Y., Lee, C.-C., Hsu, J.-H., Leu, W.-M., and Meng, M. efficient hydrolysis of gluten-derived celiac disease-triggering immunogenic peptides by a bacterial serine protease from Bukholderia gladioli. 2021. Biomolecules, 11, pp: 451- 466. doi.org/10.3390/biom11030451.