Rullo Ornella J, Woo Jennifer M P, Parsa Miriam F, Hoftman Alice D C, Maranian Paul, Elashoff David A, Niewold Timothy B, Grossman Jennifer M, Hahn Bevra H, McMahon Maureen, McCurdy Deborah K, Tsao Betty P
Arthritis Res Ther. 2013 Jan 23;15(1):R18. doi: 10.1186/ar4150.
Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.
cOPN and cNGAL were measured in prospectively followed pSLE (n=42) and adult SLE (aSLE; n=23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).
Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P=0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r=0.51 and 0.52, P=0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P=0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P=0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).
High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.
骨桥蛋白（OPN）被认为是通过I型干扰素（IFN）受体信号传导调节Th17的介质，并参与组织修复部位的巨噬细胞活性。本研究评估了循环血浆OPN（cOPN）升高是否先于儿童系统性红斑狼疮（pSLE）器官损伤的发生，并将其与循环血浆中性粒细胞明胶酶相关脂质运载蛋白（cNGAL）进行比较，后者是SLE疾病活动增加的一个预测指标。
对前瞻性随访的pSLE患者（n = 42）、成人SLE（aSLE；n = 23）患者及年龄匹配的对照者测量cOPN和cNGAL。分别使用调整后的平均SLE疾病活动指数（SLEDAI）（AMS）和SLICC/ACR损伤指数（SDI）评估时间调整后的累积疾病活动度和疾病损伤。
与对照组相比，pSLE和aSLE患者的cOPN和cNGAL均升高。cNGAL在SLEDAI恶化前3 - 6个月出现升高（P = 0.04），但与6个月时的AMS增加无关。高基线cOPN与高IFNα活性及抗核酸自身抗体的表达相关，与6个月时的AMS呈正相关（pSLE和aSLE中r分别为0.51和0.52，P分别为0.001和0.01），且与pSLE患者12个月时的SDI增加相关（P = 0.001）。使用单因素和多因素逻辑回归分析，pSLE患者SDI变化的危险因素为cOPN（比值比7.5，95%置信区间[2.9 - 20]，P = 0.03），而非cNGAL、累积泼尼松用量、疾病持续时间、免疫抑制药物使用、性别或种族。在生成基线cOPN对12个月期间SDI增加的SLE患者的指示的受试者操作特征（ROC）曲线时，曲线下面积（AUC）为0.543（95%置信区间0.347 - 0.738；阳性预测值95%，阴性预测值38%）。
SLE患者，尤其是pSLE患者，循环OPN水平升高先于累积疾病活动度增加和器官损伤，其作为不良预后预测指标的价值应在大型纵向队列中进一步验证。
