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巨噬细胞移动抑制因子(MIF)与少关节型幼年特发性关节炎(o-JIA):MIF启动子多态性与关节内糖皮质激素反应的关联

Macrophage migration inhibitory factor (MIF) and oligoarticular juvenile idiopathic arthritis (o-JIA): association of MIF promoter polymorphisms with response to intra-articular glucocorticoids.

作者信息

Vivarelli M, D'Urbano L E, Insalaco A, Lunt M, Jury F, Tozzi A E, Ravelli A, Martini A, Donn R, De Benedetti F

机构信息

Direzione Scientifica, Pediatria II Reumatologia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

出版信息

Clin Exp Rheumatol. 2007 Sep-Oct;25(5):775-81.

Abstract

OBJECTIVES

To address the clinical relevance of macrophage migration inhibitory factor (MIF) promoter polymorphisms in oligoarticular juvenile idiopathic arthritis (o-JIA) by evaluating their associations with serum and SF MIF levels, with response to intra-articular glucocorticoid injections and with outcome of the disease.

METHODS

Seventy-five Caucasian patients with o-JIA were studied. Alleles of the -794 CATT variable number of tandem repeats (VNTR) and of the -173 G/C single nucleotide polymorphism (SNP) were identified by capillary electrophoresis following fluorescently labelled PCR and by allelic discrimination assay, respectively. MIF levels were measured by ELISA. The association of MIF promoter polymorphisms with polyarticular extension, Childhood Health Assessment Questionnaire (CHAQ) score at the last follow-up visit and occurrence of chronic anterior uveitis was evaluated only in patients with a follow up > 5 years.

RESULTS

Neither of the MIF promoter polymorphisms was associated with serum MIF levels, nor with the long-term outcome of o-JIA. The -173 G/C SNP was significantly associated with both SF MIF levels and duration of response to intra-articular glucocorticoid injection. Carriers of a MIF -173 C allele were 4 times more likely to relapse within 3 months. No association was found between the different MIF CATT alleles and both SF MIF levels and duration of response to intra-articular glucocorticoids.

CONCLUSION

Our study shows the clinical relevance of the MIF -173 G/C SNP in o-JIA and suggests that the -173 C allele may represent a predictor of poor response to intra-articular glucocorticoid treatment.

摘要

目的

通过评估巨噬细胞移动抑制因子(MIF)启动子多态性与血清和滑膜液MIF水平、关节内注射糖皮质激素的反应以及疾病转归之间的关联,探讨其在少关节型幼年特发性关节炎(o-JIA)中的临床相关性。

方法

对75例白种人o-JIA患者进行研究。分别通过荧光标记PCR后的毛细管电泳和等位基因鉴别分析,鉴定-794 CATT串联重复序列(VNTR)和-173 G/C单核苷酸多态性(SNP)的等位基因。采用酶联免疫吸附测定法(ELISA)检测MIF水平。仅在随访时间>5年的患者中评估MIF启动子多态性与多关节扩展、末次随访时儿童健康评估问卷(CHAQ)评分以及慢性前葡萄膜炎发生情况之间的关联。

结果

MIF启动子多态性与血清MIF水平均无关联,也与o-JIA的长期转归无关。-173 G/C SNP与滑膜液MIF水平以及关节内注射糖皮质激素的反应持续时间均显著相关。MIF -173 C等位基因携带者在3个月内复发的可能性高4倍。未发现不同的MIF CATT等位基因与滑膜液MIF水平以及关节内糖皮质激素反应持续时间之间存在关联。

结论

我们的研究显示了MIF -173 G/C SNP在o-JIA中的临床相关性,并提示-173 C等位基因可能是关节内糖皮质激素治疗反应不佳的一个预测指标。

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