Hull Keith M, Shoham Nitza, Chae Jae Jin, Aksentijevich Ivona, Kastner Daniel L
Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Curr Opin Rheumatol. 2003 Jan;15(1):61-9. doi: 10.1097/00002281-200301000-00011.
The authors review the genes, and their respective proteins, responsible for eight autoinflammatory conditions. Familial Mediterranean fever is caused by mutations in pyrin, which is the prototype of a new family of proteins belonging to the death-domain superfamily. This new group of proteins, which regulate apoptosis, inflammation, and cytokine processing, share an approximately 90-amino-acid N-terminal sequence called the PYRIN domain. Mutations in another PYRIN domain protein, termed cryopyrin, are responsible for three clinically defined illnesses, Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and NOMID/CINCA. A related protein encoded by the gene is responsible for the Mendelian disorder, Blau syndrome, and also predisposes to Crohn disease. The gene responsible for PAPA syndrome has recently been identified as, and preliminary results from the authors' laboratory also implicate its protein product in these pathways. Lastly, the authors discuss the broadening genetic and clinical spectrum of TRAPS, an autoinflammatory syndrome resulting from mutations in the 55-kDa receptor for tumor necrosis factor.
作者们回顾了导致八种自身炎症性疾病的基因及其各自的蛋白质。家族性地中海热由吡啉基因突变引起，吡啉是死亡结构域超家族新蛋白质家族的原型。这一新的蛋白质组调节细胞凋亡、炎症和细胞因子加工，它们共享一个约90个氨基酸的N端序列，称为PYRIN结构域。另一种名为冷吡啉的PYRIN结构域蛋白的突变导致三种临床定义的疾病，即穆克-韦尔斯综合征、家族性寒冷性自身炎症综合征和新生儿多系统炎症疾病/慢性婴儿神经皮肤关节综合征。该基因编码的一种相关蛋白导致孟德尔疾病——布劳综合征，并且也易患克罗恩病。最近已确定导致PAPA综合征的基因，作者实验室的初步结果也表明其蛋白质产物参与了这些途径。最后，作者们讨论了肿瘤坏死因子55 kDa受体突变导致的自身炎症综合征——肿瘤坏死因子受体相关周期性综合征（TRAPS）不断扩大的遗传和临床谱。
