Garnier-Lengliné H, Malamut G, Cerf-Bensussan N, Ruemmele F M
Université Paris Descartes, 75006 Paris, France.
Pathol Biol (Paris). 2013 Jun;61(3):e61-4. doi: 10.1016/j.patbio.2011.03.008. Epub 2011 Oct 28.
Celiac disease (CD) is a chronic inflammatory enteropathy caused by the ingestion of gluten. A safe and efficient but unpleasant treatment exists for CD in form of a strict gluten-free diet. Thus, there is a need for new treatment strategies, which are based on the improved and advanced understanding of the pathophysiology of CD. The first strategy consists in reducing or even eliminating major antigenic motifs in gluten, responsible for the inflammatory reaction. The use of less immunogenic wheat was suggested but this seems rather difficult to realize. However, a complete digestion of the immunogenic parts of gluten looks very promising. This can be obtained by the use of polymers, capable to sequester gluten proteins or even better via the exogenous administration of propyl-endopeptidases, with two different enzymes under development. Another approach could be the use of inhibitors of tissue transglutaminase, a strategy which is under clinical investigation. Alternatively, inhibition of the site of liaison of immunostimulatory peptides with HLA molecules was suggested and is also under investigation in vivo. For patients suffering from refractory sprue, the inhibition of IL15 might be of therapeutic interest with the hope to improve the fatal outcome of many of these patients. However, the ultimate treatment approach is in form of prevention and the role of infectious agents, such as Rotavirus, in disease onset has to be considered.
乳糜泻(CD)是一种由摄入麸质引起的慢性炎症性肠病。对于CD,有一种安全有效的但令人不适的治疗方法,即严格的无麸质饮食。因此,需要基于对CD病理生理学的更深入和先进理解的新治疗策略。第一种策略是减少甚至消除麸质中负责炎症反应的主要抗原基序。有人提出使用免疫原性较低的小麦,但这似乎很难实现。然而,完全消化麸质的免疫原性部分看起来很有前景。这可以通过使用能够螯合麸质蛋白的聚合物来实现,或者甚至更好地通过外源性给予丙基内肽酶来实现,目前有两种不同的酶正在研发中。另一种方法可能是使用组织转谷氨酰胺酶抑制剂,这一策略正在进行临床研究。或者,有人提出抑制免疫刺激肽与HLA分子的结合位点,并且也正在进行体内研究。对于患有难治性口炎性腹泻的患者,抑制IL15可能具有治疗意义,希望能改善许多这类患者的致命结局。然而,最终的治疗方法是预防,并且必须考虑感染因子(如轮状病毒)在疾病发病中的作用。