Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Rheumatology (Oxford). 2012 Oct;51(10):1785-9. doi: 10.1093/rheumatology/kes151. Epub 2012 Jul 4.
Microarray studies have provided insight into the pathogenesis of systemic JIA and have opened new avenues for therapy. Data on the pathogenesis of the enthesitis-related arthritis (ERA) category of JIA are limited, thus we studied the expression profile of ERA patients' peripheral blood and SF mononuclear cells (PBMCs and SFMCs, respectively). PBMCs from healthy subjects were used as controls.
RNA from PBMCs of ERA patients (n=17) and healthy controls (n=8) and seven ERA SFMCs were converted to labelled cRNA and hybridized to Illumina Human WG-6_v3_BeadChip chips. Expression profiles were analysed using GeneSpring software. Selected genes of interest were validated by real-time PCR.
There was no significant difference in PBMC gene expression of ERA and control groups. However, there was a significant difference between expression profiles of SFMCs and PBMCs of patients with ERA, with 131 genes being overexpressed and 216 being underexpressed in SFMCs. Among genes involved with immune function, cluster of differentiation (CD)1b, CD1d, MHC class II alpha and beta chain, and soluble CD163 were overexpressed, whereas genes related to NK cell function, namely, Granzyme H, killer cell lectin-like receptor subfamily F member 1, killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail (KIR3DL3), natural killer group 7 (NKG7) and other genes like CD244, CD248 and Fas apoptotic inhibitory molecule 3 (FAIM3) were underexpressed.
ERA SFMCs had a distinct gene expression profile from PBMCs and had higher expression of genes associated with antigen presentation, scavenger function, chemotaxis and proteases, whereas genes involved in NK cell function, cell adhesion and inhibitors of apoptosis were underexpressed.
微阵列研究为全身型幼年特发性关节炎的发病机制提供了深入了解，并为治疗开辟了新途径。关于幼年特发性关节炎（JIA）中附着点相关关节炎（ERA）类别的发病机制的数据有限，因此我们研究了 ERA 患者外周血和滑液单核细胞（PBMC 和 SFMC）的表达谱。健康受试者的 PBMC 用作对照。
将 ERA 患者（n=17）和健康对照（n=8）的 PBMC 和 7 个 ERA SFMC 的 RNA 转化为标记的 cRNA，并与 Illumina Human WG-6_v3_BeadChip 芯片杂交。使用 GeneSpring 软件分析表达谱。通过实时 PCR 验证了感兴趣的选定基因。
ERA 和对照组 PBMC 基因表达无显著差异。然而，ERA 患者 SFMC 和 PBMC 的表达谱之间存在显著差异，SFMC 中 131 个基因表达上调，216 个基因表达下调。在涉及免疫功能的基因中，CD1b、CD1d、MHC 类 II ɑ 和 β 链和可溶性 CD163 表达上调，而与 NK 细胞功能相关的基因，即 Granzyme H、杀伤细胞凝集素样受体亚家族 F 成员 1、杀伤细胞免疫球蛋白样受体，三个结构域，长胞质尾（KIR3DL3）、自然杀伤组 7（NKG7）和其他基因，如 CD244、CD248 和 Fas 凋亡抑制分子 3（FAIM3）表达下调。
ERA SFMC 的基因表达谱与 PBMC 明显不同，具有更高的与抗原呈递、吞噬功能、趋化和蛋白酶相关的基因表达，而与 NK 细胞功能、细胞黏附及凋亡抑制剂相关的基因表达下调。
