Division of Internal Medicine, IRCCS Istituto Clinico Humanitas, via A. Manzoni 56, Rozzano, 20089, Milan, Italy.
Clin Rev Allergy Immunol. 2012 Jun;42(3):342-54. doi: 10.1007/s12016-011-8253-3.
Several crucial issues remain open in our understanding of primary biliary cirrhosis (PBC), an autoimmune liver disease targeting the small- and medium-sized intrahepatic bile ducts. These issues include the high tissue specificity of the autoimmune injury despite the nontraditional autoantigens found in all mitochondria recognized by PBC-associated autoantibodies, the causes of the commonly observed pruritus, and the disease etiology per se. In all these fields, there has been recent interest secondary to the use of large-scale efforts (such as genome-wide association studies) that were previously considered poorly feasible in a rare disease such as PBC as well as other intuitions. Accordingly, there are now fascinating theories to explain the onset and severity of pruritus due to elevated autotaxin levels, the peculiar apoptotic features of bile duct cells to explain the tissue specificity, and genomic and epigenetic associations contributing to disease susceptibility. We have arbitrarily chosen these four aspects as the most promising in the PBC recent literature and will provide herein a discussion of the recent data and their potential implications.
原发性胆汁性肝硬化（PBC）是一种针对中小肝内胆管的自身免疫性肝病，我们对其仍有许多尚未解决的问题。这些问题包括尽管 PBC 相关自身抗体识别的所有线粒体都存在非传统的自身抗原，但自身免疫损伤仍具有高度的组织特异性、常见瘙痒的原因以及疾病本身的病因。在所有这些领域，由于使用了大规模的研究方法（如全基因组关联研究），人们对这些领域产生了浓厚的兴趣，而这些方法以前被认为在 PBC 等罕见疾病中不太可行，此外还有其他一些直觉因素。因此，现在有一些引人入胜的理论可以解释由于升高的自分泌酶水平导致的瘙痒的发生和严重程度、解释组织特异性的胆管细胞的特殊凋亡特征，以及与疾病易感性相关的基因组和表观遗传关联。我们随意选择了这四个方面作为 PBC 近期文献中最有前途的方面，并将在此讨论最近的数据及其潜在影响。
