Braun Jonathan, Targan Stephan R
UCLA Hospital Center for Health Sciences, Los Angeles, CA, USA.
Adv Exp Med Biol. 2006;579:209-18. doi: 10.1007/0-387-33778-4_13.
The integrity of the intestinal mucosa depends on a functional coordination of the epithelium, lumenal microorganisms, and the local immune system. The mammalian immune system is superbly organized for innate and adaptive recognition of microbial antigens, a defensive capacity that must be balanced against the tissue damage produced by immune activity to preserve normal intestinal function. Inflammatory bowel disease (IBD) is generally thought to reflect an impairment in this balance, due to a combination of host genetic traits that shift the balance of immune and epithelial function to commensal microbiota, and perhaps the composition or activity of certain microbial elements as well. There has been much progress defining the fundamental disorders of these host traits, immunologic processes, and microbial targets in inflammatory bowel disease. Other fields of clinical and geologic microbiology are teaching us about the dynamic interaction of commensal bacteria with their host environment. These lines of investigation have revealed not only important insights about inflammatory bowel disease (IBD) pathogenesis, but also defined technologies and tools useful for its diagnosis and clinical management. This review focuses on these advances at the translational interface. We will first consider the innate anti-microbial response, centering on the utility of NOD2 genotyping for predicting disease susceptibility, prognosis, and therapeutic response profile. We will then turn to the adaptive anti-microbial response, focusing on the application of antibodies to fungal and bacterial species and products for Crohn's disease (CD) diagnosis and prognosis, and immunogenetics of T cell immunosuppression management. Finally, we will describe autoimmune mechanisms in IBD, with particular attention to autoantibodies in IBD diagnosis and infliximab responsiveness. We will conclude with the concept of multiparameter analysis of patients, to refine patient characterization and stratification in diagnosis and clinical management.
肠道黏膜的完整性取决于上皮细胞、管腔微生物和局部免疫系统之间的功能协调。哺乳动物的免疫系统在对微生物抗原的先天性和适应性识别方面组织得极为出色，这种防御能力必须与免疫活动产生的组织损伤相平衡，以维持正常的肠道功能。炎症性肠病（IBD）通常被认为反映了这种平衡的受损，这是由于宿主遗传特征的组合将免疫和上皮功能的平衡转向共生微生物群，或许还与某些微生物成分的组成或活性有关。在确定炎症性肠病中这些宿主特征、免疫过程和微生物靶点的基本紊乱方面已经取得了很大进展。临床和地质微生物学领域的其他研究正在让我们了解共生细菌与其宿主环境之间的动态相互作用。这些研究不仅揭示了关于炎症性肠病（IBD）发病机制的重要见解，还确定了对其诊断和临床管理有用的技术和工具。本综述重点关注这些在转化界面的进展。我们首先将考虑先天性抗微生物反应，重点是NOD2基因分型在预测疾病易感性、预后和治疗反应方面的效用。然后我们将转向适应性抗微生物反应，重点是针对真菌和细菌物种及产物的抗体在克罗恩病（CD）诊断和预后中的应用，以及T细胞免疫抑制管理的免疫遗传学。最后，我们将描述IBD中的自身免疫机制，特别关注IBD诊断和英夫利昔单抗反应性中的自身抗体。我们将以对患者进行多参数分析的概念作为结尾，以优化诊断和临床管理中的患者特征描述和分层。
