Zöliakie: Neue pharmakologische Therapien

Was ist neu?

Gründe für eine supportive pharmakologische Therapie

Trotz der glutenfreien Diät leiden 30–50% der diagnostizierten Betroffenen weiterhin an Beschwerden – mit Zeichen der Entzündung, u.a. wegen unvermeidbarer minimaler Gluten-Kontaminationen im Alltag.

Strategien für eine supportive pharmakologische Therapie

Vielversprechende therapeutische Ansätze sind zurzeit in klinischer Phase-2-Entwicklung, u.a. ein Hemmstoff der intestinalen TG2, blockierende Antikörper gegen Interleukin-15 oder Ox40-Ligand, die Verbesserung der intestinalen Barriere mittels eines Sirtuin-6-Agonisten, sowie nanopartikuläre Therapien, die über Adressierung der Milz oder Leber eine Toleranz gegenüber Gluten induzieren können.

Abstract

Coeliac disease is the most common chronic inflammatory disease of the small intestine, with a prevalence of around 1% almost worldwide. It is caused by the consumption of cereals containing gluten (wheat, spelt, rye, barley). The initial diagnosis is made in equal proportions in children and adults. Classic symptoms are abdominal pain, diarrhea, malabsorption with anemia or osteoporosis, weight loss, and in children failure to thrive. Non-specific symptoms such as poor performance, headaches and joint pain are also common. Often undetected and untreated, coeliac disease can lead to serious complications, and up to 30% of adult coeliac patients suffer from associated autoimmune diseases, including thyroid and rheumatoid diseases or type 1 diabetes. The pathogenesis of coeliac disease is well studied. Incompletely digested gluten peptides reach the immune system of the intestinal mucosa and activate glute-reactive T cells, which lead to inflammation and atrophy of the absorptive villi. The prerequisite for the development of coeliac disease is the carrier status for HLA-DQ2 or DQ8, as well as the enzyme and coeliac disease autoantigen transglutaminase-2 expressed in the intestine, which modifies the gluten peptides by deamidation and thus increases their binding to HLA-DQ2/DQ8 and subsequent T-cell activation. Despite the gluten-free diet, 30–50% of diagnosed patients continue to suffer from symptoms with signs of inflammation, partly due to unavoidable minimal gluten contamination in everyday life. Supportive pharmacological therapy is therefore urgently needed. Promising therapeutic approaches are currently in clinical phase 2 development, including an inhibitor of intestinal TG2, blocking antibodies against interleukin-15 or Ox40 ligand, the improvement of the intestinal barrier using a sirtuin-6 agonist, as well as nanoparticular therapies that can induce tolerance to gluten by addressing the spleen or liver.

Schlüsselwörter

Zöliakie - HLA-DQ2/HLA-DQ8 - Transglutaminase - Toleranz - transglutaminase - tolerance

Keywords

celiac disease - HLA-DQ2/HLA-DQ8

Publikationsverlauf

Artikel online veröffentlicht:
21. Februar 2025

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