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血清白细胞介素-18作为预测儿童期起病系统性红斑狼疮患者长期肾脏预后的生物标志物。

Serum IL-18 as biomarker in predicting long-term renal outcome among pediatric-onset systemic lupus erythematosus patients.

作者信息

Wu Chao-Yi, Yang Huang-Yu, Yao Tsung-Chieh, Liu Su-Hsun, Huang Jing-Long

机构信息

Division of Allergy, Asthma, and Rheumatology, Chang Gung Children's Hospital Chang Gung University, College of Medicine Department of Nephrology Department of Family Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

出版信息

Medicine (Baltimore). 2016 Oct;95(40):e5037. doi: 10.1097/MD.0000000000005037.

Abstract

An urge of biomarker identification is needed to better monitor lupus nephritis (LN) disease activity, guide clinical treatment, and predict patient's long-term outcome. With the proinflammatory effect and its association with inflammasomes, the significance of interleukin-18 (IL-18) among pediatric-onset systemic lupus erythematous (pSLE) patient, especially, its importance in predicting long-term renal outcome was investigated.In a pSLE cohort of 96 patients with an average follow-up period of 10.39 ± 3.31 years, clinical data and laboratory workups including serum IL-18 were collected at time of disease onset and 6 months after treatment despite their initial renal status. Through Cox regression analysis, the parameters at baseline and at 6 months posttreatment were carefully analyzed.Average age of all cases was 12.74 ± 3.01 years old and 65 of them underwent renal biopsy at the time of diagnosis. Nine subjects (9.38%) progressed to end-stage renal disease (ESRD) and 2 cases (2.08%) died during follow-up. Through multivariate analysis, serum IL-18 level 6 months posttreatment was found to be the most unfavorable factor associating poor clinical outcome despite patient's initial renal status. In addition, the presentation of serum IL-18 in its correlation with SLE global disease activity as well as the presence and severity of LN were all significant (P < 0.001, P = 0.03, and P = 0.02, respectively). The histological classification of LN, however, was not associated with the level of IL-18 among the pSLE patients (P = 0.64).The role of serum IL-18 as biomarker representing global disease activity and status of renal flares among pSLE population was shown for the first time. Additionally, we have identified IL-18 at 6 months posttreatment a novel marker for long-term renal outcome prediction.

摘要

为了更好地监测狼疮性肾炎(LN)的疾病活动、指导临床治疗并预测患者的长期预后,需要鉴定生物标志物。鉴于白细胞介素-18(IL-18)的促炎作用及其与炎性小体的关联,本研究调查了其在儿童期系统性红斑狼疮(pSLE)患者中的意义,尤其是其在预测长期肾脏预后方面的重要性。在一个由96例患者组成的pSLE队列中,平均随访期为10.39±3.31年,在疾病发作时以及治疗后6个月收集了临床数据和实验室检查结果,包括血清IL-18,无论其初始肾脏状况如何。通过Cox回归分析,仔细分析了基线和治疗后6个月的参数。所有病例的平均年龄为12.74±3.01岁,其中65例在诊断时接受了肾活检。9名受试者(9.38%)进展为终末期肾病(ESRD),2例(2.08%)在随访期间死亡。通过多变量分析,发现治疗后6个月的血清IL-18水平是与不良临床结局相关的最不利因素,无论患者的初始肾脏状况如何。此外,血清IL-18与SLE整体疾病活动的相关性以及LN的存在和严重程度均具有显著性(分别为P<0.001、P = 0.03和P = 0.02)。然而,LN的组织学分类与pSLE患者中IL-18水平无关(P = 0.64)。首次证明了血清IL-18作为代表pSLE人群整体疾病活动和肾脏发作状态的生物标志物的作用。此外,我们确定治疗后6个月的IL-18是预测长期肾脏预后的新标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9504/5059068/eee1f983cc35/medi-95-e5037-g002.jpg

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