Department of Biomedical Engineering, University of Houston, Houston TX, USA.
Rheumatology and Rehabilitation Department, Faculty of Medicine, Minia University, Minia, Egypt.
Lupus. 2021 Aug;30(9):1394-1404. doi: 10.1177/09612033211016100. Epub 2021 May 14.
To evaluate the performance of 4 plasma protein markers for detecting disease activity in childhood-onset systemic lupus erythematosus (SLE) patients.
Eighty-three consecutive pediatric patients fulfilling ≥4 ACR criteria for SLE and twenty-five healthy controls were prospectively recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using SLEDAI-2000 score. Fifty-seven patients had clinically active SLE (SLEDAI score ≥4, or having a flare).
The plasma concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE. Plasma Axl levels were significantly higher in active renal versus active non-renal SLE patients. Levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores. Levels of Axl, IFGBP4 and sTNFR2 inversely correlated with plasma complement C3 levels. Only plasma Axl and ferritin levels correlated with degree of proteinuria. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA antibody titer or decreased C3. Ferritin and IGFBP4 levels were more specific for concurrent active lupus nephritis than anti-dsDNA or C3. Plasma ferritin was the best monitor of global SLE activity, followed by C3 then Axl, while both Axl and C3 were best monitors of clinical lupus nephritis activity.
In childhood-onset SLE patients, plasma ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these plasma markers should be explored further in longitudinal cohorts of SLE patients.
评估 4 种血浆蛋白标志物在儿童起病系统性红斑狼疮（SLE）患者中检测疾病活动度的性能。
前瞻性招募 83 例符合≥4 项 ACR 标准的儿童患者，并招募 25 名健康对照者进行 4 种蛋白标志物的血清学检测，这 4 种蛋白标志物由抗体包被的微阵列筛选确定，即 Axl、铁蛋白、IGFBP4 和 sTNFR2。采用 SLEDAI-2000 评分评估 SLE 疾病活动度。57 例患者有活动性 SLE（SLEDAI 评分≥4，或有发作）。
与无活动性 SLE 相比，活动性 SLE 患者的血浆 Axl 和铁蛋白浓度明显升高。与活动性非肾性 SLE 患者相比，活动性肾性 SLE 患者的血浆 Axl 水平显著升高。Axl、铁蛋白和 IGFBP4 水平与 SLEDAI 评分显著相关。Axl、IGFBP4 和 sTNFR2 水平与血浆补体 C3 水平呈负相关。仅 Axl、IGFBP4 和 sTNFR2 水平与蛋白尿程度相关。与升高的抗 dsDNA 抗体滴度或降低的 C3 相比，这些标志物在检测同时存在的 SLE 活性方面更特异，但敏感性较低。铁蛋白和 IGFBP4 水平在检测同时存在的活动性狼疮肾炎方面比抗 dsDNA 或 C3 更特异。血浆铁蛋白是监测整体 SLE 活动度的最佳指标，其次是 C3，然后是 Axl，而 Axl 和 C3 都是监测临床狼疮肾炎活动度的最佳指标。
在儿童起病 SLE 患者中，与传统指标相比，血浆铁蛋白和 Axl 能更好地识别疾病活动度，无论是全身性还是肾脏性。应在 SLE 患者的纵向队列中进一步探索这些血浆标志物的性能。
