PDF(Pubmed)
Abstract：
UNASSIGNED: Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects.
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.
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.
摘要：
■系统性幼年特发性关节炎（sJIA）是一种严重的炎症，在儿童期发病。它是零星的，但其定型先天免疫反应的要素可能是由效应大小较小的常见变异体和效应较大的罕见变异体遗传编码的.
■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。
■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。
