Advances in understanding and managing celiac disease: Pathophysiology and treatment strategies

Abstract

In this editorial, we comment on an article published in the recent issue of the World Journal of Gastroenterology. Celiac disease (CeD) is a disease occurring in genetically susceptible individuals, which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain, diarrhea, and malnutrition. Therefore, patients often need a lifelong gluten-free diet, which greatly affects the quality of life and expenses of patients. The gold standard for diagnosis is intestinal mucosal biopsy, combined with serological and genetic tests. At present, the lack of safe, effective, and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis, and it is difficult to find a perfect target to solve the multi-level needs of patients. In this editorial, we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

Keywords: Aspergillus niger prolyl endoprotease; Celiac disease; Gluten-free diet; Human leukocyte antigen; Immunotherapy; Pathology; Treatment.

Figure 1

Pathophysiological mechanisms of celiac disease. Gluten or gliadin crosses the epithelial cells, and after the deamidation by transglutaminase-2 (TG2), they become easier to be recognized by antigen presenting cells (APCs) expressing HLA-DQ2/8. APCs could secrete interleukin (IL)-15 which causes damage to epithelial cells directly or through activation of intraepithelial lymphocytes expressing natural killer cell receptor. Also, APCs present the deamidated polypeptides complex to CD4⁺ T cells which further secrete interferon-γ and IL-21 to cause damage to epithelial cells. In another way, CD4⁺ T cells activate B cells to differentiate into plasma cells with secretion of antibodies against gluten, TG2, and deamidated polypeptides complex. TG2: Transglutaminase-2; IL: Interleukin; HLA: Human leukocyte antigen; APC: Antigen presenting cells; TCR: T cell receptor; IELs: Intraepithelial lymphocytes; IFN-γ: Interferon-γ; NKG2D: Natural killer cell receptor.