UNASSIGNED: Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS).
UNASSIGNED: Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making.
■基因组研究确定了sJIA的独特遗传结构。将II类HLA基因座鉴定为最强的sJIA危险因素首次引起了人们对sJIA中T淋巴细胞和适应性免疫机制的关注。认识到HLA-DRB*15等位基因与药物诱导的超敏反应和sJIA-LD的发展密切相关,从而增强了人类白细胞抗原(HLA)基因座的重要性。在IL1RN位点,遗传变异与sJIA的风险有关,也可能预测对anakinra的无反应。最后,罕见的遗传变异可能在疾病并发症中起关键作用,例如患有sJIA样疾病的家庭中的纯合LACC1突变,和噬血细胞淋巴组织细胞增多症(HLH)基因变异在一些儿童巨噬细胞活化综合征(MAS)。
sJIA的遗传和基因组分析为sJIA的基本发现和并发症提供了巨大的希望,并可能有助于指导个性化医疗和治疗决策。