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Zöliakie

Pathogenese, Klinik, Epidemiologie, Diagnostik, Therapie

Celiac disease

Pathogenesis, clinics, epidemiology, diagnostics, therapy

  • Leitthema
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Die Zöliakie wird durch den Verzehr glutenhaltiger Getreide (Weizen, Dinkel, Roggen, Gerste) hervorgerufen. Mit einer Prävalenz um 1 % ist sie die häufigste nichtinfektiöse chronisch-entzündliche Erkrankung des Darmes weltweit. Sie kann sich in jedem Alter manifestieren: klassisch mit Bauchschmerzen, Diarrhoe, Gedeihstörungen oder Gewichtsverlust, überwiegend jedoch mit indirekten Auswirkungen einer Malabsorption (Anämie, Osteoporose) oder mit assoziierten Autoimmunerkrankungen, z. B. der Bauchspeicheldrüse (Typ-1-Diabetes), der Schilddrüse oder der Haut (Dermatitis herpetiformis). Die Pathogenese der Zöliakie ist gut untersucht. So wird das Speicherprotein Gluten nur unvollständig verdaut und aktiviert in der Dünndarmschleimhaut der Patienten entzündliche T‑Zellen, die zu einer Atrophie der resorptiven Villi führen. Voraussetzung hierfür ist das Vorliegen einer genetischen Prädisposition (die Moleküle HLA-DQ2 [HLA – human lymphocyte antigen] oder HLA-DQ8 auf antigenpräsentierenden Immunzellen). Ferner verstärkt das im Darm freigesetzte Enzym Gewebetransglutaminase (TG2) durch Deamidierung die Immunogenität des Glutens. Der Antikörpertest gegen das Autoantigen TG2 ist einer der besten diagnostischen Tests in der Medizin und sichert, gemeinsam mit endoskopisch gewonnenen Dünndarmbiopsien, die Diagnose der Zöliakie. Trotzdem ist die Erkrankung bei 80–90 % der Betroffenen immer noch unerkannt. Die unbehandelte Zöliakie kann zu schweren Komplikationen führen. Hierzu gehören die Folgen der Malabsorption, Malignome (u. a. das intestinale T‑Zell-Lymphom) und wahrscheinlich auch die Bahnung von Autoimmunerkrankungen. Die Therapie, eine strikt glutenfreie Diät (GFD), ist schwierig und nicht immer wirksam. Alternative, unterstützende pharmakologische Therapien werden dringend benötigt und sind derzeit in Entwicklung.

Abstract

Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80–90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.

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Authors and Affiliations

  1. Institut für Translationale Immunologie, Zentrum für Zöliakie und Dünndarmerkrankungen und Forschungszentrum für Immuntherapie (FZI), Universitätsmedizin, Johannes Gutenberg-Universität Mainz, Langenbeckstr.1, 55131, Mainz, Deutschland

    Detlef Schuppan

  2. Division of Gastroenterology and Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 02215, Boston, MA, USA

    Detlef Schuppan

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Correspondence to Detlef Schuppan.

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Interessenkonflikt

D. Schuppan gibt an, dass er Patentinhaber für den Antikörpertest gegen Transglutaminase 2 ist. Hier besteht kein Interessenkonflikt.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Schuppan, D. Zöliakie. Bundesgesundheitsbl 59, 827–835 (2016). https://doi.org/10.1007/s00103-016-2364-1

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