Kirino Yohei, Nakajima Hideaki
Department of Stem Cell and Immune Regulation, Yokohama City University, Graduate School of Medicine, Japan.
Intern Med. 2019 May 1;58(9):1199-1207. doi: 10.2169/internalmedicine.2035-18. Epub 2019 Jan 10.
Patients with Behçet's disease (BD) suffer from episodic ocular and mucocutaneous attacks, resulting in a reduced quality of life. The phenotype of Japanese BD has been changing over the past 20 years, and the rate of human leukocyte antigen (HLA)-B*51-positive complete type is decreasing while that of intestinal type is increasing. This phenotypical evolution may be related to changes in as-yet-unknown environmental factors, as the immigration influx in Japan is low. Mechanisms discovered by genome-wide association studies include ERAP1-mediated HLA class I antigen bounding pathway, autoinflammation, Th17 cells, natural killer cells, and polarized macrophages, a similar genetic architecture to Crohn's disease, ankylosing spondylitis, and psoriasis. As for treatments, management guidelines have been implemented, and the development of tumor necrosis factor (TNF) inhibitors is markedly improving the outcome of BD, but evidence supporting treatment for special-type BD is limited. The classification of BD into distinct clusters based on clinical manifestations and genetic factors is crucial to the development of optimized medicine.
白塞病（BD）患者会遭受间歇性眼部和黏膜皮肤发作，导致生活质量下降。在过去20年中，日本BD的表型一直在变化，人类白细胞抗原（HLA）-B*51阳性完全型的比例在下降，而肠道型的比例在上升。由于日本的移民流入较少，这种表型演变可能与尚不明确的环境因素变化有关。全基因组关联研究发现的机制包括ERAP1介导的HLA I类抗原结合途径、自身炎症、Th17细胞、自然杀伤细胞和极化巨噬细胞，其遗传结构与克罗恩病、强直性脊柱炎和银屑病相似。至于治疗，已经实施了管理指南，肿瘤坏死因子（TNF）抑制剂的开发显著改善了BD的治疗效果，但支持特殊类型BD治疗的证据有限。根据临床表现和遗传因素将BD分为不同的簇对于优化药物的开发至关重要。
