系统性红斑狼疮患者血清骨硬化蛋白及Dickkopf-1水平与病情严重程度的关系

Relationships of serum sclerostin and DKK-1 levels with severity of disease in patients with systemic lupus erythematosus

  • 摘要:
    目的 探讨系统性红斑狼疮(SLE)患者血清骨硬化蛋白(Sclerostin)及Dickkopf-1(DKK-1)水平与疾病严重程度的关系。
    方法 选取2020年1月—2022年1月收治的126例SLE患者为SLE组,依据SLE疾病活动度评分(SLEDAI)将SLE组患者又分为轻度活动组(n=46)、中度活动组(n=42)和高度活动组(n=38);选取同期健康体检者70例为对照组。采用酶联免疫吸附实验检测2组血清Sclerostin和DKK-1水平。采用Pearson相关性分析探讨SLE组血清Sclerostin、DKK-1水平与生化指标的相关性。采用多因素Logistic回归模型分析影响SLE患者疾病严重程度的因素。采用受试者工作特征(ROC)曲线评价血清Sclerostin、DKK-1评估SLE患者疾病严重程度的价值。
    结果 SLE组血清Sclerostin、DKK-1、红细胞沉降率、抗双链DNA抗体(抗dsDNA抗体)高于对照组,白细胞计数、血红蛋白、淋巴细胞计数、血小板、补体C3及C4水平低于对照组,差异有统计学意义(P < 0.01)。Pearson相关性分析结果显示, SLE组患者血清Sclerostin、DKK-1水平与白细胞计数、血红蛋白、淋巴细胞计数、血小板、补体C3及C4呈负相关(P < 0.01), 与红细胞沉降率、抗dsDNA抗体呈正相关(P < 0.01)。高度活动组患者血清Sclerostin、DKK-1水平高于中度活动组和轻度活动组,中度活动组患者血清Sclerostin、DKK-1水平高于轻度活动组,差异均有统计学意义(P < 0.05)。血清Sclerostin、DKK-1升高是影响SLE疾病严重程度的独立危险因素。血清Sclerostin联合DKK-1对SLE疾病高度活动预测的曲线下面积(AUC)为0.919(95%CI: 0.862~0.956), 高于血清Sclerostin、DKK-1的0.833(Z=4.978, 95%CI: 0.809~0.851, P < 0.001)、0.841(Z=4.213, 95%CI: 0.810~0.867, P < 0.001)。
    结论 SLE患者血清Sclerostin、DKK-1表达水平升高,二者与SLE疾病严重程度有关,是影响SLE疾病严重程度的独立危险因素。血清Sclerostin联合DKK-1对SLE疾病严重程度具有较高的预测价值。

     

    Abstract:
    Objective To explore the relationships of serum sclerostin and Dickkopf-1 (DKK-1) levels with severity of disease in patients with systemic lupus erythematosus (SLE).
    Methods A total of 126 patients with SLE from January 2020 to January 2022 were selected as SLE group, and the patients in the SLE group were divided into mild active group (n=46), moderate active group (n=42) and severe active group (n=38) according to SLE disease activity index (SLEDAI) score; 70 healthy people in the same period were selected as control group. The serum levels of Sclerostin and DKK-1 in both groups were detected by enzyme-linked immunosorbent assay. Pearson correlation analysis was used to explore the correlations of the serum Sclerostin and DKK-1 levels with biochemical indicators in the SLE group. Multivariate Logistic regression model was used to analyze the factors affecting the severity of disease in SLE patients. Receiver operating characteristic (ROC) curve was used to assess the values of serum Sclerostin and DKK-1 in evaluating the severity of disease in SLE patients.
    Results Serum levels of Sclerostin, DKK-1, erythrocyte sedimentation rate and anti-double stranded DNA antibody (anti-dsDNA antibody) in the SLE group were significantly higher than those in the control group, while the levels of leukocyte count, hemoglobin, lymphocyte count, platelet, complement C3 and C4 were significantly lower than those in the control group (P < 0.01). Pearson correlation analysis results showed that serum levels of Sclerostin and DKK-1 in the SLE group were significantly negatively correlated with leukocyte count, hemoglobin, lymphocyte count, platelet, complement C3 and complement C4 (P < 0.01), and were significantly positively correlated with erythrocyte sedimentation rate and anti-dsDNA antibody (P < 0.01). The serum levels of Sclerostin and DKK-1 in the severe active group were significantly higher than those in the moderate active group and mild active group, and the serum levels of Sclerostin and DKK-1 in the moderate active group were significantly higher than those in the mild active group (P < 0.05). Elevated levels of serum Sclerostin and DKK-1 were the independent risk factors affecting the severity of SLE. The area under the curve (AUC) of serum Sclerostin combined with DKK-1 for predicting high activity of SLE was 0.919 (95%CI, 0.862 to 0.956), which was significantly higher than 0.833 of serum Sclerostin (Z=4.978, 95%CI, 0.809 to 0.851, P < 0.001) and 0.841 of DKK-1 (Z=4.213, 95%CI, 0.810 to 0.867, P < 0.001).
    Conclusion The increased expression levels of serum Sclerostin and DKK-1 in SLE patients are related to the severity of SLE, and are the independent risk factors affecting the severity of SLE. The combination of serum Sclerostin and DKK-1 has a high predictive value for the severity of SLE.

     

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