The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis
The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis
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DOI：
10.1002/art.23437
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Rubartelli, Anna
中科院分区：
文献类型：
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作者：
Gattorno, Marco;Piccini, Alessandra;Rubartelli, Anna
目标。目的：探讨白细胞介素-1 （IL-1）阻断治疗对全身性幼年特发性关节炎（JIA）的临床疗效及体外IL-1 β和IL-18分泌的影响。22例系统iconset JIA患者接受IL-1受体拮抗剂（IL-1Ra） anakinra治疗。来自18名患者和20名健康供体的单核细胞被不同的toll样受体配体激活。采用Western blotting和酶联免疫吸附法分析细胞内和分泌的IL-1 β和IL-18。10例全身性JIA患者对阿那金表现出显著的反应，并被归类为完全应答者。11例患者反应不完全或无反应，1例患者无法根据反应进行分类。与完全缓解或无缓解的患者相比，完全缓解者活动关节数量较少（P = 0.02），绝对中性粒细胞计数增加（P = 0.02）。体外对各种刺激的IL-1 β和IL-18分泌没有增加，与治疗效果无关。同样，来自全身性JIA患者的单核细胞分泌IL-1Ra也未受损。观察到暴露于外源性ATP后IL-1 β分泌水平总体较低，与治疗反应性或疾病活动性无关。根据患者对IL-1阻断的反应，可以确定两种全身性JIA亚群。这两个亚群似乎具有一些不同的临床特征。全身性RA患者单核细胞的IL-1 β和IL-18体外分泌不增加，与治疗结果和疾病活动无关。
Objective. To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1 beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA).Methods. Twenty-two patients with systemiconset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands. Intracellular and secreted IL-1 beta and IL-18 were analyzed by Western blotting and enzyme-linked immunosorbent assay.Results. Ten patients with systemic-onset JIA exhibited a dramatic response to anakinra and were classified as complete responders. Eleven patients had an incomplete response or no response, and I patient could not be classified in terms of response. Compared with patients who had an incomplete response or no response, complete responders had a lower number of active joints (P = 0.02) and an increased absolute neutrophil count (P = 0.02). In vitro IL-1 beta and IL-18 secretion in response to various stimuli was not increased and was independent of treatment efficacy. Likewise, secretion of IL-1Ra by monocytes from patients with systemic-onset JIA was not impaired. An overall low level of IL-1 beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity.Conclusion. Two subsets of systemic-onset JIA can be identified according to patient response to IL-1 blockade. The 2 subsets appear to be characterized by some distinct clinical features. In vitro secretion of IL-1 beta and IL-18 by monocytes from patients with systemic-onset RA is not increased and is independent of both treatment outcome and disease activity.