Clinical Relevance of Autoantibodies against Interleukin-2 in Patients with Systemic Lupus Erythematosus

系统性红斑狼疮患者抗白细胞介素-2 自身抗体的临床意义

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作者:Miao Shao, Xiao-Lin Sun, He Sun, Jing He, Rui-Jun Zhang, Xia Zhang, Zhan-Guo Li

Background

Increased serum autoantibodies against interleukin-2 (anti-IL-2 autoantibodies) were reported in patients with systemic lupus erythematosus (SLE) and in patients receiving IL-2 therapy. This study aimed to explore the clinical relevance of serum anti-IL-2 autoantibodies and the interactions between low-dose IL-2 therapy and serum anti-IL-2 autoantibodies.

Conclusions

Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE. Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production. 血清IL-2抗体在系统性红斑狼疮中临床及实验室相关性研究摘要背景:系统性红斑狼疮(SLE)的患者血清IL-2抗体水平升高。本研究探索了血清IL-2抗体在系统性红斑狼疮患者中的水平及其意义。 方法:收集152例SLE患者及100例年龄性别匹配的健康体检者血清,并在第10周对其中75例SLE患者进行随访,所有的随访患者均接受激素和免疫抑制剂的治疗,有46例随访患者在原有免疫抑制剂治疗的基础上加用低剂量IL-2治疗。用ELISA方法检测患者及健康体检者血清IL-2抗体水平,分析血清IL-2抗体在SLE患者中的意义。 结果:SLE患者血清IL-2抗体水平比正常人高 (37.54 [27.88, 60.74] AU vs. 32.58 [23.63, 45.23] AU, P=0.006),且阳性率也高于正常人 (18.4% vs 5.0%, P=0.002)。有脱发的SLE患者血清IL-2抗体升高 (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P=0.033),但是狼疮肾炎的患者血清IL-2抗体水平较低 (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P=0.001)。血清IL-2抗体与血清免疫球蛋白IgA (r=0.229, P=0.005)、IgG (r= 0.327, P<0.001)、IgM (r= 0.164, P=0.050) 水平呈正相关。接受低剂量IL-2治疗的SLE患者治疗后血清IL-2抗体水平和阳性率与传统治疗组相比也无明显差异。此外,在低剂量IL-2治疗的患者中,比较症状改善者与无改善者之间血清IL-2抗体水平也未发现明显统计学差异。 结论:系统性红斑狼疮的患者血清IL-2抗体水平升高且与疾病严重程度相关。低剂量IL-2治疗不增加IL-2抗体的产生。.

Methods

Serum samples were collected from 152 SLE patients and 100 age- and gender-matched healthy controls (HCs). Among them, 75 SLE patients were followed up for 10 weeks, and all of them were treated with corticosteroids, antimalarials, and/or immunosuppressants. Forty-six out of the 75 SLE patients received low-dose IL-2 therapy additionally. Clinical and laboratory parameters were collected at baseline and week 10. Serum anti-IL-2 autoantibodies were determined by enzyme-linked immunosorbent assay.

Results

Compared with HCs, median levels and positive rates of serum anti-IL-2 autoantibodies were higher in SLE patients (32.58 [23.63, 45.23] arbitrary unit [AU] vs. 37.54 [27.88, 60.74] AU, P = 0.006, and 5.0% vs. 18.4%, P = 0.002, respectively). Compared to those without the corresponding disorders, serum anti-IL-2 autoantibody was increased in patients with alopecia (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P = 0.033), but it was decreased in those with lupus nephritis (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P = 0.001). Moreover, serum anti-IL-2 autoantibody was positively correlated with serum IgA (r = 0.229, P = 0.005), total IgG (r = 0.327, P < 0.001), and total IgM (r = 0.164, P = 0.050). Treatment with exogenous IL-2 was not significantly associated with serum anti-IL-2 autoantibody. In addition, no significant difference was found in serum anti-IL-2 autoantibody between responders and nonresponders to low-dose IL-2 therapy. Conclusions: Serum anti-IL-2 autoantibody was increased and associated with disease severity in SLE. Exogenous low-dose IL-2 did not significantly induce anti-IL-2 autoantibody production. 血清IL-2抗体在系统性红斑狼疮中临床及实验室相关性研究摘要背景:系统性红斑狼疮(SLE)的患者血清IL-2抗体水平升高。本研究探索了血清IL-2抗体在系统性红斑狼疮患者中的水平及其意义。 方法:收集152例SLE患者及100例年龄性别匹配的健康体检者血清,并在第10周对其中75例SLE患者进行随访,所有的随访患者均接受激素和免疫抑制剂的治疗,有46例随访患者在原有免疫抑制剂治疗的基础上加用低剂量IL-2治疗。用ELISA方法检测患者及健康体检者血清IL-2抗体水平,分析血清IL-2抗体在SLE患者中的意义。 结果:SLE患者血清IL-2抗体水平比正常人高 (37.54 [27.88, 60.74] AU vs. 32.58 [23.63, 45.23] AU, P=0.006),且阳性率也高于正常人 (18.4% vs 5.0%, P=0.002)。有脱发的SLE患者血清IL-2抗体升高 (49.79 [36.06, 64.95] AU vs. 35.06 [25.40, 58.46] AU, P=0.033),但是狼疮肾炎的患者血清IL-2抗体水平较低 (31.71 [22.60, 43.25] AU vs. 44.15 [31.43, 68.52] AU, P=0.001)。血清IL-2抗体与血清免疫球蛋白IgA (r=0.229, P=0.005)、IgG (r= 0.327, P<0.001)、IgM (r= 0.164, P=0.050) 水平呈正相关。接受低剂量IL-2治疗的SLE患者治疗后血清IL-2抗体水平和阳性率与传统治疗组相比也无明显差异。此外,在低剂量IL-2治疗的患者中,比较症状改善者与无改善者之间血清IL-2抗体水平也未发现明显统计学差异。 结论:系统性红斑狼疮的患者血清IL-2抗体水平升高且与疾病严重程度相关。低剂量IL-2治疗不增加IL-2抗体的产生。.

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