狼疮性肾炎患者外周血炎症和免疫调节相关分子水平变化及其预测预后的价值

Change in levels of molecules related to inflammation and immune regulation in peripheral blood of patients with lupus nephritis and their values in predicting prognosis

  • 摘要:
    目的 分析狼疮性肾炎(LN)患者外周血高迁移率族蛋白B1(HMGB1)、白细胞介素-32(IL-32)、基质金属蛋白酶-9(MMP-9)/基质金属蛋白酶抑制剂-1(TIMP-1)水平变化及其预测预后的价值。
    方法 选取2021年10月—2023年6月收治的86例LN患者为研究对象, 均给予诱导治疗6个月,再根据病情缓解情况分为缓解组(66例)和无反应组(20例)。比较2组基线资料、HMGB1、IL-32、MMP-9/TIMP-1水平变化及降低率; 分析外周血HMGB1、IL-32、MMP-9/TIMP-1水平降低率与治疗应答的偏相关性以及预测治疗应答的价值; 比较不同HMGB1、IL-32、MMP-9/TIMP-1降低率患者病情进展情况。
    结果 缓解组治疗1、3个月后HMGB1、IL-32、MMP-9/TIMP-1水平较治疗前降低,差异有统计学意义(P < 0.05); 缓解组治疗1、3个月后HMGB1、IL-32、MMP-9/TIMP-1水平低于无反应组,差异有统计学意义(P < 0.05); 缓解组治疗1、3个月后HMGB1、IL-32、MMP-9/TIMP-1水平降低率高于无反应组,差异有统计学意义(P < 0.05)。偏相关性分析显示, HMGB1、IL-32、MMP-9/TIMP-1水平降低率与治疗应答独立相关(P < 0.05); 治疗1、3个月后, HMGB1、IL-32、MMP-9/TIMP-1水平降低率联合预测缓解的曲线下面积(AUC)分别为0.910、0.932, 其中治疗3个月后联合预测的AUC最大,差异有统计学意义(P < 0.05)。根据治疗3个月后ROC曲线分析的最佳截断值将患者分为高降低率亚组和低降低率亚组, HMGB1、IL-32、MMP-9/TIMP-1高降低率亚组患者病情进展率低于低降低率亚组,差异有统计学意义(P < 0.05)。
    结论 LN患者外周血HMGB1、IL-32、MMP-9/TIMP-1高水平变化与治疗应答、病情进展显著相关,治疗1、3个月后HMGB1、IL-32、MMP-9/TIMP-1联合预测LN患者治疗应答的价值较高。

     

    Abstract:
    Objective To analyze the change in levels of high mobility group box 1 protein (HMGB1), interleukin-32 (IL-32), matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in peripheral blood of patients with lupus nephritis (LN) and their values in predicting prognosis.
    Methods A total of 86 patients with LN from October 2021 to June 2023 were selected and treated with induction therapy for 6 months. Based on remission status of the disease, patients were divided into remission group (n=66) and non-responder group (n=20). Baseline data, change in levels and reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1, and the partial correlation of reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in peripheral blood with treatment response as well as their predictive values for treatment response were compared between the two groups. Disease progression was compared between patients with different reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1.
    Results HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group decreased significantly at 1 and 3 months after treatment compared to before treatment (P < 0.05); the levels of HMGB1, IL-32 and MMP-9/TIMP-1 in the remission group were significantly lower than those in the non-responder group at 1 and 3 months after treatment (P < 0.05); the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels in the remission group were significantly higher than those in the non-responder group at 1 and 3 months after treatment (P < 0.05). Partial correlation analysis showed that the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were independently significantly correlated with treatment response (P < 0.05). One and three months after treatment, the values of the area under the curve (AUC) for the combined prediction of remission by the reduction rates of HMGB1, IL-32 and MMP-9/TIMP-1 levels were 0.910 and 0.932 respectively, with the AUC being the largest at 3 months after treatment (P < 0.05). Patients were divided into high and low reduction rate subgroups based on theoptimal cut-off value from the ROC curve analysis at 3 months after treatment, and the disease progression rate was significantly lower in the high reduction rate subgroup than in the low reduction rate subgroup for HMGB1, IL-32 and MMP-9/TIMP-1 (P < 0.05).
    Conclusion The great change in levels of HMGB1, IL-32 and MMP-9/TIMP-1 in peripheral blood of LN patients is significantly correlated with treatment response and disease progression, and the combined detections of HMGB1, IL-32 and MMP-9/TIMP-1 levels at 1 and 3 months after treatment have high value in predicting the treatment response of LN patients.

     

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