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[白介素-10受体拮抗剂治疗系统性红斑狼疮患者中消退素D1的临床意义]

[The clinical significance of resolvin D1 in patients with systemic lupus erythematosus treated with Belimumab].

作者信息

Wang M J, Zhou L, Wu J, Wang Y, Ren T, Yin Y F, Cao J, Cheng T

机构信息

Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou 215000, China.

Department of Nephrology, the First Affiliated Hospital of Soochow University, Suzhou 215000, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2025 Feb 4;105(5):358-363. doi: 10.3760/cma.j.cn112137-20240717-01640.

Abstract

To explore the changes and significance of resolvin D1 (RvD1) in the treatment of systemic lupus erythematosus (SLE) with Belimumab. The clinical data from patients with moderate to severe disease activity SLE who received oral stable doses of glucocorticoids (≤10 mg/d) and/or immunosuppressants for more than 3 months at the outpatient or inpatient department of the First Affiliated Hospital of Soochow University from January 2022 to November, 2023 were retrospectively collected. All patients were treated with 10 mg/kg intravenous infusion of Belimumab. The medication was administered once on the 1st, 15th, and 29th days, and then every 4 weeks for a total of 24 weeks and 8 doses. Peripheral blood plasma before and after treatment were collected, and RvD1 levels before and after treatment were detected using enzyme-linked immunosorbent assay (ELISA). According to the guidelines, SLE patients were divided into kidney involvement group and kidney non-involvement group; the patients were further divided into a blood system involvement group and a blood system non-involvement group; according to the SLE Disease Activity Index (SLEDAI), the patients were divided into moderate activity group and severe activity group. After 24 weeks of treatment, the patients were divided into complete remission group, low disease activity group, and no remission group according the treatment effects. The changes in plasma RvD1 levels in each group before and after treatment with Belimumab were analyzed, and their correlation with various activity indicators of SLE was checked too. A total of 81 patients were included, of which 15 were male and 66 were female, with an average age of (33.14±8.27) years. At baseline, plasma RvD1 levels in SLE patients were negatively correlated with SLEDAI scores (=-0.642, <0.001) and anti dsDNA antibody levels (=-0.623, =0.012). There was no significant difference in plasma RvD1 level [(, )] between SLE patients with renal involvement (=50) and those without renal involvement (=31) [73.27 (45.16, 122.12) ng/L vs 58.32 (32.29, 94.33) ng/L, =0.365]. There was no significant difference in plasma RvD1 level between SLE patients with hematological involvement (=40) and those without hematological involvement (=41) [74.78 (47.01, 121.67) ng/L vs 42.88 (30.05, 76.76) ng/L, =0.277]. The plasma RvD1 level in the moderate activity group (=51) was significantly higher than that in the severe activity group (=30) [104.76 (65.65, 135.34) ng/L vs 55.86 (37.53, 81.35) ng/L, =0.002]. After 24 weeks of treatment with Belimumab, plasma RvD1 levels in the complete remission group (=10) were both significantly higher than those in the low disease activity group (=61) and the non-remission group (=10) [196.48 (123.08, 236.33) ng/L vs 98.87 (63.35, 110.23) ng/L and 77.68 (41.73, 128.55) ng/L, respectively, =0.001]. After the treatment, the plasma RvD1 levels in both the complete remission group and the low disease activity group increased significantly when compared to those before the treatment [98.23 (40.45, 107.19) ng/L vs 176.48 (123.08, 226.33) ng/L and 65.27 (31.76, 94.35) ng/L vs 98.87 (63.35, 110.23) ng/L, both <0.05]. Further analysis revealed that all the patients of complete remission group after treatment were from the moderate disease activity group before treatment, and the plasma RvD1 level in the complete remission group was significantly higher than that in the low disease activity group before the treatment [98.23 (40.45, 127.19) vs 65.27 (31.76, 94.35) ng/L] (=0.022). The plasma RvD1 level significantly increased after treatment with Belimumab in SLE patients, patients with higher plasma RvD1 level before treatment have better efficacy with Belimumab.

摘要

探讨用贝利尤单抗治疗系统性红斑狼疮(SLE)时消退素D1(RvD1)的变化及意义。回顾性收集2022年1月至2023年11月在苏州大学附属第一医院门诊或住院部接受口服稳定剂量糖皮质激素(≤10mg/d)和/或免疫抑制剂治疗3个月以上的中度至重度疾病活动期SLE患者的临床资料。所有患者均接受10mg/kg贝利尤单抗静脉输注。分别于第1、15和29天给药1次,然后每4周给药1次,共24周8剂。收集治疗前后外周血血浆,采用酶联免疫吸附测定(ELISA)检测治疗前后RvD1水平。根据指南,将SLE患者分为肾脏受累组和肾脏未受累组;患者进一步分为血液系统受累组和血液系统未受累组;根据SLE疾病活动指数(SLEDAI),将患者分为中度活动组和重度活动组。治疗24周后,根据治疗效果将患者分为完全缓解组、低疾病活动组和未缓解组。分析贝利尤单抗治疗前后各组血浆RvD1水平的变化,并检查其与SLE各项活动指标的相关性。共纳入81例患者,其中男性15例,女性66例,平均年龄(33.14±8.27)岁。基线时,SLE患者血浆RvD1水平与SLEDAI评分(r=-0.642,P<0.001)和抗双链DNA抗体水平(r=-0.623,P=0.012)呈负相关。肾脏受累的SLE患者(n=50)与未受累患者(n=31)的血浆RvD1水平[(中位数,四分位数间距)]无显著差异[73.27(45.16,122.12)ng/L对58.32(32.29,94.33)ng/L,P=0.365]。血液系统受累的SLE患者(n=40)与未受累患者(n=41)的血浆RvD1水平无显著差异[74.78(47.01,121.67)ng/L对42.88(30.05,76.76)ng/L,P=0.277]。中度活动组(n=51)的血浆RvD1水平显著高于重度活动组(n=30)[104.76(65.65,135.34)ng/L对55.86(37.53,81.35)ng/L,P=0.002]。贝利尤单抗治疗24周后,完全缓解组(n=10)的血浆RvD1水平均显著高于低疾病活动组(n=61)和未缓解组(n=10)[分别为196.48(123.08,236.33)ng/L对98.87(63.35,110.23)ng/L和77.68(41.73,128.55)ng/L,P=0.001]。治疗后,完全缓解组和低疾病活动组的血浆RvD1水平均较治疗前显著升高[98.23(40.45,107.19)ng/L对176.48(123.08,226.33)ng/L和65.27(31.76,94.35)ng/L对98.87(63.35,110.23)ng/L,均P<0.05]。进一步分析显示,治疗后完全缓解组的所有患者均来自治疗前中度疾病活动组,且完全缓解组治疗前的血浆RvD1水平显著高于低疾病活动组[98.23(40.45,127.19)对65.27(31.76,94.35)ng/L](P=0.022)。贝利尤单抗治疗后SLE患者血浆RvD1水平显著升高,治疗前血浆RvD1水平较高的患者使用贝利尤单抗疗效更好。

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