Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease.
Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease.
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DOI：
10.1136/rmdopen-2015-000097
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发表时间：
2015
期刊：
影响因子：
6.2
通讯作者：
Punzi L
中科院分区：
文献类型：
--
作者：
Caso F;Galozzi P;Costa L;Sfriso P;Cantarini L;Punzi L
最近发现的导致炎症和凋亡途径功能障碍的基因突变，已经允许识别一组疾病，被认为是单基因自身炎症综合征。其中，Blau综合征（BS）和早发性结节病（EOS）已被确定为相同的非干酪化肉芽肿形式的家族性和散发性表型。这两种疾病都是由CARD 15/NOD 2基因突变引起的，CARD 15/NOD 2基因编码细胞溶质NOD 2蛋白，细胞溶质NOD 2蛋白是调节先天免疫的关键分子之一。临床发作通常位于生命的最初几年，表型特征为同时或较少的关节、皮肤和眼部非干酪化肉芽肿性炎症，其可能与异质性全身谱相关。CARD 15/NOD 2基因也被鉴定为与克罗恩病（CD）易感性相关的基因之一，克罗恩病是一种常见的多基因炎性肉芽肿性肠病。在CD患者的肠组织中发现核因子-κB活性升高，可能是与几种CARD 15/NOD 2多态性相关的遗传原因。CARD 15/NOD 2基因中的其他取代也在最近描述的称为NOD 2相关自身炎症性疾病的疾病中发现，该疾病与BS和EOS具有若干临床特征。本文试图根据最新的证据来描述这些疾病。本文从遗传学和临床两个方面进行阐述，重点介绍了自身炎性肉芽肿性疾病中最具代表性的BS和EOS两种疾病，以扩大对这两种疾病的认识。
The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the CARD15/NOD2 gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The CARD15/NOD2 gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-κB activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several CARD15/NOD2 polymorphisms. Other substitutions in the CARD15/NOD2 gene have also been found in a recently described disorder, called NOD2-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge.