Department of Dermatology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Dermatol Ther. 2011 May-Jun;24(3):364-8. doi: 10.1111/j.1529-8019.2011.01421.x.
New drug treatment opportunities based on the results of a genome-wide association study, which implicate T cell and natural killer (NK)-cell activation pathways, are leading to new approaches in future clinical trials of alopecia areata. Special attention is being given to the UL 16-binding protein (ULBP3) gene cluster on chromosome 6q25, as these genes make the NKG2D-activating ligand or signal that can trigger the NKG2D receptor, initiating an autoimmune response. A greater expression of ULBP3 has also been found in hair follicles in scalp biopsy specimens from patients with active disease. It is now postulated that the characteristic T cell "swarm of bees" infiltrate seen in alopecia areata is the result of T cells being attracted to the hair follicle by NKG2D-activating ligands. Future treatment approaches for alopecia areata include use of drugs that: (i) block the NKGD-activating ligand and NKG2D receptor interaction, (ii) halt activated T cells, or (iii) modification of the inflammatory cytokine network. Many drugs currently being used or being evaluated for other autoimmune diseases that work through these mechanisms might prove to be very effective in alopecia areata.
基于全基因组关联研究的结果,新的药物治疗机会表明 T 细胞和自然杀伤 (NK)-细胞激活途径正在导致斑秃未来临床试验的新方法。人们特别关注染色体 6q25 上的 UL16 结合蛋白 (ULBP3) 基因簇,因为这些基因产生 NKG2D 激活配体或信号,可以触发 NKG2D 受体,引发自身免疫反应。在患有活动性疾病的头皮活检标本的毛囊中也发现了 ULBP3 的更高表达。现在推测,斑秃中可见的特征性 T 细胞“蜂群”浸润是 T 细胞被 NKG2D 激活配体吸引到毛囊的结果。斑秃的未来治疗方法包括使用以下药物:(i) 阻断 NKGD 激活配体和 NKG2D 受体相互作用,(ii) 阻止激活的 T 细胞,或 (iii) 改变炎症细胞因子网络。许多目前用于治疗其他自身免疫性疾病的药物或正在评估这些机制的药物可能在斑秃中非常有效。