Celiac disease

The disease is characterized by an inappropriate immune response leading to changes in the gut (crypt hyperplasia and villous atrophy), stomachache, malabsorption (accompanied by impaired growth in young children), diarrhea, and tiredness. Interestingly, extraintestinal symptoms represent a substantial proportion of the clinical manifestations of the disease (dermatitis herpetiformis, arthritis, neurological symptoms, anemia…) (Dieterich et al., 1998; Lindfors et al., 2019).

The basis for the diagnosis of celiac disease is a combination of serology testing and the determination of small intestinal mucosal morphology forms (e.g. endoscopy and biopsy). The most common serological tests various serological tests are EmAs (antibodies specific for TG2 in the endomysium, which is a form of perivascular connective tissue) and TG2-Ab assays (ELISA), reaching a sensitivity of 98.1% and a specificity of 94.7% in patients with biopsy-confirmed cases (Dieterich et al., 1997; Dieterich et al., 1998).

Importantly, some patients are IgA deficient and around 10% of patients are seronegative. Although for these cases the gold standard is the biopsy, other tests are:

• For patients IgA deficient, EMAs and TG2 assay with IgG, considering that IgG may be elevated due to other autoimmune diseases, and the predictive value is lower (Dieterich et al., 1998)
• HLA typing is useful as the disease is unlikely when individuals do not carry HLA-DQ2 or HLA-DQ8 (Lindfors et al., 2019).
• Detection of intestinal TG2-targeted celiac IgA isotype autoantibody deposits in intestinal mucosal tissue samples is helpful but requires frozen biopsy samples.
• Detection of T cells. A 3-day gluten challenge induces the mobilization of memory T cells reactive against gliadin, which can be detected by IFNγ enzyme-linked immunospot (ELISPOT) assay. Otherwise, T cells can be detected with HLA-DQ–gluten tetramers by flow cytometry.

Homo sapiens. Although irish setters have shown increased intestinal permeability, partial villous atrophy and intraepithelial infiltration with lymphocytes in connection with gluten in the diet. However, this disease is paroxysmal gluten-sensitive dyskinesia (PGSD) and it is connected primarily with the nervous system, not the small intestine. There is no serological test for PGSD (Lowrie et al., 2018).

Celiac disease may be considered as a public health problem as it increases the overall mortality risk, reduces quality of life and yields extensive negative economic consequences. Although majority of patients experienced a good and long life after the diagnosis, a subgroup may develop complications such as T-cell lymphoma (Lindfors et al., 2019; Dieterich et al., 1997).

Although Swedish epidemiological study of coeliac disease in the mid-1980s88 suggests that coeliac disease may be prevented by the early introduction of small quantities of gluten into the diet of young children, two systematic reviews and meta- analyses have concluded that the timing of gluten introduction and the duration or maintenance of breastfeeding do not influence the development of coeliac disease. The use of primitive wheat varieties (kamut, einkorn and others) or the use of oats to reduce the clinical symptoms have not been shown in proper trials (Lindfors et al., 2019).

About 20–50% of patients with coeliac disease have persistent or recurrent symptoms despite a long- term gluten- free diet, usually due to other gastrointestinal disorders (irritable bowel syndrome, lactose intolerance…) or inadvertent gluten exposure. To avoid this last one, US FDA in 2013 or EU 828/2014 enforced regulations to labelling products defining “gluten free” as less than 20 mg/kg when measured by an approved system for testing, normally gluten-analysis R5 ELISA (Mendez), as less than 20ppm is considered safe in celiac disease patients. Although there are a good range of products available, these products are often inadequately labelled, less palatable, and more expensive, causing non-adherence to a strict gluten free diet. Managing the disease involves an active effort from the patient to regulate feelings, actions and reactions during any social activity that involves food (Lindfors et al., 2019).

• Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D. (1997). Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 3:797-801.
• Dieterich W, Laag E, Schöpper H, Volta U, Ferguson A, Gillett H, Riecken EO, Schuppan D. (1998). Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology. 115:1317-1321.
• Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B. (2004). Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity. 21:357-366.
• Lindfors K., Ciacci C., Kurppa K., Lundin K. E. A., Makharia G. K., Mearin M. L., Murray J. A., Verdu E. F., Kaukinen K. (2019). Coeliac disease. Nature Reviews Disease Primers, 5(1), Article 3. https://doi.org/10.1038/s41572-018-0054-z
• Lowrie M, Garden OA, Hadjivassiliou M, Sanders DS, Powell R, L Garosi L. (2018). Characterization of Paroxysmal Gluten‐Sensitive Dyskinesia in Border Terriers Using Serological Markers. J Vet Intern Med. Feb 9;32(2):775–781. doi: 10.1111/jvim.15038