Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Nat Immunol. 2018 Jul;19(7):685-695. doi: 10.1038/s41590-018-0130-2. Epub 2018 Jun 20.
Risk factors for most autoimmune diseases are multifactorial genetic variants modified by environmental risk factors. Type 1 diabetes and celiac disease share high-risk HLA haplotypes, and the prevalence of both diseases has increased in many regions during the past half century. Unknown environmental factors are suspected to have increased the disease penetrance. Celiac disease depends on immune responses to dietary gluten, whereas the environmental risk factors for type 1 diabetes are not yet clear. Here, we consider the shared heritable genetic factors and review evidence of the dietary and microbial exposures, particularly in early life, that might influence the pathogenesis of one or both diseases. A deeper mechanistic understanding of the environmental factors responsible for increased risk of these diseases should provide opportunities to manipulate exposure in children carrying defined risk markers and thus prevent and attenuate disease, as well as to identify new therapeutic strategies for patients.
大多数自身免疫性疾病的风险因素是受环境风险因素影响的多因素遗传变异。1 型糖尿病和乳糜泻共享高风险 HLA 单倍型，在过去半个世纪中，许多地区这两种疾病的患病率都有所增加。疑似环境因素增加了疾病的外显率。乳糜泻依赖于对膳食谷蛋白的免疫反应，而 1 型糖尿病的环境风险因素尚不清楚。在这里，我们考虑了共同的遗传因素，并回顾了饮食和微生物暴露的证据，特别是在生命早期，这些因素可能影响一种或两种疾病的发病机制。对导致这些疾病风险增加的环境因素的更深入的机制理解，应该为携带明确风险标志物的儿童提供操纵暴露的机会，从而预防和减轻疾病，并为患者确定新的治疗策略。
