Lerner Aaron
Pediatric Gastroenterology and Nutrition Unit, Carmel Medical Center, B Rapapport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Harefuah. 2012 Jun;151(6):358-61, 377.
Celiac disease is a common autoimmune disease affecting 1% of the Western populations. It is an inappropriate immune response, in genetically susceptible patients to dietary wheat, rye, barley and oats. Treatment involves a Lifelong gluten-free diet that predisposes to low compliance due to limited variety, high cost and low palatability, imposing social pressure and affecting quality of life. The result is an urgent need for alternative therapeutic strategies. Based on the growing actual knowledge on the intestinal inflammatory cascade, mucosal immunology and genetics of celiac disease, new attractive potential therapies are emerging. Possibilities include: searching for low immunogenic wheat variants or strains pretreated with enzymes or binders for lower toxicity. Other strategies involve decreasing transepithelial uptake or dampening of the adaptive immune response by transglutaminase inhibitors or blockage of the HLA groove and immune modulation to shift the TH1 to TH2 profile. Developing biological therapy aims to decrease intestinal homing, adhesion and activity of inflammatory cells, counteract the pro-inflammatory cytokines, clonal intestinal T cells or mesenchymal stem cell replacement or mitogenic intestinal repair safety, cost, affordability and clinical effectiveness are of prime concern. Most of the above strategies showed promising results ex-vivo. The future will highlight the in-vivo winner.
乳糜泻是一种常见的自身免疫性疾病,影响着1%的西方人群。它是一种不适当的免疫反应,发生在对饮食中的小麦、黑麦、大麦和燕麦具有遗传易感性的患者身上。治疗方法包括终身无麸质饮食,但由于种类有限、成本高和适口性差,这种饮食往往导致依从性较低,还会带来社会压力并影响生活质量。因此,迫切需要替代治疗策略。基于对乳糜泻肠道炎症级联反应、黏膜免疫学和遗传学的实际认识不断增加,新的有吸引力的潜在治疗方法正在出现。可能性包括:寻找低免疫原性的小麦变体或用酶或结合剂预处理以降低毒性的菌株。其他策略包括通过转谷氨酰胺酶抑制剂减少经上皮摄取或减弱适应性免疫反应,或阻断HLA凹槽以及进行免疫调节以将TH1型转变为TH2型。开发生物疗法旨在减少炎症细胞的肠道归巢、黏附和活性,对抗促炎细胞因子、克隆性肠道T细胞,或进行间充质干细胞替代或促有丝分裂性肠道修复,安全性、成本、可承受性和临床有效性是首要关注点。上述大多数策略在体外实验中显示出了有希望的结果。未来将凸显出体内实验的优胜者。