Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity.
Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity.
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DOI：
10.1186/s12969-015-0047-3
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发表时间：
2015-11-20
期刊：
影响因子：
--
通讯作者：
Junge G
中科院分区：
文献类型：
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作者：
Nirmala N;Brachat A;Feist E;Blank N;Specker C;Witt M;Zernicke J;Martini A;Junge G
成人发病的斯蒂尔氏病（AOSD）是一种罕见的自身炎症性疾病，类似于系统性青少年特发性关节炎（SJIA）。AOSD和SJIA具有重叠的系统性临床特征，提示两种临床表型代表了不同发病年龄的同一疾病连续体。为了进一步表征AOSD和SJIA在分子水平上的相似性，研究人员利用先前在SJIA中发现的2个应答基因集来研究canakinumab对SJIA患者白细胞介素(IL)-1β抑制的应答基因在IL-1β靶向治疗前的活期AOSD患者中相对于健康受试者的表现。与健康受试者相比，canakinumab治疗后SJIA患者中下调的所有基因在canakinumab治疗前在大多数活动性AOSD患者中上调。少数轻度AOSD患者的基因表达模式与健康受试者相似，这是意料之中的。基因表达模式与中性粒细胞计数的比较显示中性粒细胞数量升高与canakinumab应答基因上调之间存在相关性。相应地，在SJIA患者中，canakinumab治疗后上调的大多数基因在大多数AOSD患者中下调。这些结果进一步支持斯蒂尔氏病连续体的概念，包括儿童/青少年发病（SJIA）和成人发病（AOSD）形式。
Adult-onset Still’s disease (AOSD), a rare autoinflammatory disorder, resembles systemic juvenile idiopathic arthritis (SJIA). The superimposable systemic clinical features of AOSD and SJIA suggest both clinical phenotypes represent the same disease continuum with different ages of onset. To further characterize the similarity between AOSD and SJIA at the molecular level, 2 previously identified response gene sets in SJIA were used to investigate how genes that respond to interleukin (IL)-1β inhibition with canakinumab in SJIA patients behave in AOSD patients with active disease prior to IL-1β targeting therapy, relative to healthy subjects. All genes downregulated in SJIA patients following canakinumab treatment were upregulated in most patients with active AOSD prior to canakinumab treatment, relative to healthy subjects. A few patients with milder AOSD had expectedly gene-expression patterns that resembled those in healthy subjects. Comparison of the gene-expression patterns with neutrophil counts showed a correlation between elevated neutrophil numbers and upregulation of canakinumab-responsive genes. Correspondingly, most genes upregulated following canakinumab treatment in patients with SJIA patients were downregulated in the majority of AOSD patients. These results further support the concept of a Still’s disease continuum that includes both a pediatric/juvenile onset (SJIA) and adult onset (AOSD) form.