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Celiac disease (CD), also known as gluten-sensitive enteropathie (GSE), is a genetically determined, T-cell mediated, chronic inflammatory condition of the small intestine which has an autoimmune component. The symptoms vary and differ between adults and children.
Total villous atrophy, once considered the only histologic finding compatible with a diagnosis of CD, is now considered only the extreme of a continuous spectrum of tissue damage that can be detected during the acute phase of the disease. In half of all adult cases there are no bowel symptoms (like recurring gastrointestinal pains, swollen stomach, diarrhoea) but other indications:¹
The persistence of mucosal injury with or without typical symptoms can lead to serious complications, and gastrointestinal malignancies (particularly lymphomas). Celiac disease together with H. pylori infection and IBD may predispose for GI lymphomas.²
Who should be tested?
Testing is indicated for subjects with symptoms suggestive of CD, as well as for those with CD-associated diseases (e.g. insulin dependant diabetes mellitus, autoimmune thyroiditis, genetic syndroms, dermal or neurological signs).³ᴵ⁴
Diagnostic: Detecting antibodies against transglutaminases
Tissue transglutaminase (tTG/TG2) is the target of specific autoimmune responses and has been used to develop innovative diagnostic tools. But the discovery of tTG as the main endomysial autoantigen failed to explain why only a proportion of gluten sensitivity patients show other symptoms (e.g. of dermatitis herpetiformis, DH) and why there is a difference in the antigenic repertoire between CD and the other known diseases associated with gluten sensitivity. It turned out that the epidermal transglutaminase (eTG/TG3), an isoform of the enzyme, rather than tTG is the autoantigen in DH.⁵ A positive result for anti-eTG-IgA in bloodstream can be an indicator for a skin biopsy to confirm DH.⁶ For neuroceliac disease (Gluten-ataxia, -neuropathy and -encepahlopathy) biopsy is no option. Therefore, only the detection of anti-nTG(TG6)-antibodies are indicative for this manifestation of celiac disease:
Dermatitis herpetiformis
Dermatitis herpetiformis (DH) is currently considered the specific cutaneous manifestation of Celiac Disease (CD).⁷ Epidermal transglutaminase (eTG, TG3 or TGe) is an enzyme expressed in the epidermis that is homologous but not identical to tissue transglutaminase (tTG). Patients with DH produce two IgA antibody populations against eTG: The first population binds exclusively eTG, whereas the second one crossreacts with both eTG and tTG.⁵ High affinity anti-eTG IgA maintained by gluten is present in DH patients and not in patients suffering from CD.⁵ᴵ⁸ Therefore, eTG IgA-titer determination (ELISA) may be a sensitive diagnostic test for DH and serves as an additional primary screening tool in patients with relevant symptoms of DH and a clinical history of gluten-sensitive enteropathy...
Neuro-celiac disease
In 10% of patients with proven celiac disease, neurological disorders appear in the course of the disease in addition to the gastrointestinal complaints.⁹ On the one hand, it could be explained by cross-reactivity of the auto-antibodies against htTG with neuronal transglutaminase (hnTG), and on the other hand, auto antibodies are formed directly against other members of the transglutaminase family, in particular against hnTG.¹⁰ In particular patients who do not eat gluten-free, produce a higher amount of antibodies against hnTG. By not following a gluten free diet (GFD), the risk is increased for a neurological manifestation of gluten intolerance.¹¹ This risk increases with the time of exposure to gluten¹²...
Gluten Immunogenic Peptides (GIP)
All products that contain gluten in any form – even in small amounts – can cause a severe intolerance reaction in sensitized and genetically predisposed people. Currently, the only therapy for this disease complex is a diet in which all gluten-containing foods are avoided. However, there are many situations in which the strict diet can pose a major challenge for patients: When visiting restaurants and travelling, it is only possible to adhere to the diet to a limited extent; others do not want to permanently change their everyday family, work and leisure activities because of their illness.¹³ Learn more about how the determination of gluten-immunogenic peptides can support not only the treating physician but also the patient during therapy...
References
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[2] Shirwaikar Thomas A, Schwartz M, Quigley E (2019) Gastrointestinal lymphoma: the new mimic. BMJ Open Gastroenterol 6(1): e000320. doi: 10.1136/bmjgast-2019-000320.
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[5] Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N (2002) Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J Exp Med 195(6):747-57. doi: 10.1084/jem.20011299.
[6] Betz J, Grover RK, Ullman L (2021) Evaluation of IgA epidermal transglutaminase ELISA in suspected dermatitis herpetiformis patients. Dermatol Online J 27(4):13030/qt81r9142k.
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[8] Rose C, Armbruster FP, Ruppert J, Igl BW, Zillikens D, Shimanovich I (2009) Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet. J Am Acad Dermatol 61(1):39-43. doi: 10.1016/j.jaad.2008.12.037. Epub 2009 Apr 2.
[9] Hadjivassiliou M et al. (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 64(3):332-43
[10] Boscolo S et al. (2010) Anti transglutaminase antibodies cause ataxia in mice. PLoS One 5(3): e9698.
[11] Lindfors K et al. (2011) IgA-class autoantibodies against neuronal transglutaminase, TG6 in celiac disease: no evidence for gluten dependency. Clin Chim Acta 412(13-14):1187-1189
[12] De Leo L et al. (2018) Anti-transglutaminase 6 Antibody Development in Children With Celiac Disease Correlates With Duration of Gluten Exposure. J Pediatr Gastroenterol Nutr 66(1): 64-68
[13] Casellas F, Rodrigo L, Lucendo AJ, Fernández-Bañares F, Molina-Infante J, Vivas S, Rosinach M, Dueñas C, López-Vivancos J (2015) Benefit on health-related quality of life of adherence to gluten-free diet in adult patients with celiac disease. Rev Esp Enferm Dig 107(4):196-201.
