Leptin在系统性红斑狼疮患者中表达及与CD4^+ CD25^+ Foxp3^+ Tregs细胞相关性的研究

Correlation between the expression of leptin in patients with systemic lupus erythematosus and CD4^+ CD25^+ Foxp3^+ Tregs

目的研究瘦素(Leptin)在系统性红斑狼疮(SLE)患者中表达情况及与疾病活动度、临床和实验室指标及CD4^+CD25^+Foxp3^+Tregs的关系,探讨Leptin对Treg调节作用及对SLE发病的影响。方法选择47例女性SLE患者作为SLE组,另选择年龄、体质量指数与实验组相当的健康体检者25例作为健康组,采用ELISA方法和流式细胞学技术(FACS)测定2组血浆Leptin水平及外周血Tregs百分率,比较SLE组不同疾病活动度患者Leptin水平并分析Leptin与疾病活动评分(SLEDAI)、临床表现、实验室指标及外周血Tregs的相关性。分离SLE患者外周血单个核细胞(PBMC),FACS分析在有/无抗Leptin条件下体外培养40h及80h Tregs百分率。结果 SLE组血浆Leptin水平显著高于健康组(P<0.05);SLE患者中度活动组及重度活动组血浆Leptin水平均高于健康组(P均<0.05),且重度活动组Leptin水平明显高于中度及轻度活动组(P均<0.05);SLE患者血浆Leptin水平与SLEDAI呈正相关(r=0.316 2,P=0.030 4),而与外周血Tregs呈明显负相关(r=0.288 8,P=0.049 0);健康组血浆Leptin水平与外周血Tregs则无明显相关性(r=0.121 9,P=0.561 5)。体外实验中抗Leptin处理后Tregs数量显著增加(P<0.05)。结论 SLE患者血清Leptin水平显著升高,在某种程度上疾病活动程度越高,其血清Leptin水平越高;Leptin可能通过抑制Tregs增殖参与SLE发病。

Objective It is to observe the correlation between the expression of leptin in patients with systemic lupus erythematosus （SLE） and CD4^＋CD25^＋Foxp3^＋ Tregs, and investigate the influence of leptin on the regulation of Treg and the pathogenesis of SLE. Methods The serum leptin level and percent of peripheral blood CD4^＋CD25^＋Foxp3^＋ Tregs from 47 cases of lupus patients and 25 cases of healthy controls matched in age and body mass index （BMI） were assayed by enzyme linked immunosorbent assay （ELISA） technique and fluorescence activating cell sorter （FACS）. The levels of leptin in different groups of lupus disease activity were compared, and the correlations between leptin and SLEDAI, clinical or laboratory indicators, and Tregs were analyzed respectively. Peripheral blood mononuclear cells （PBMCs） isolated from SLE patients were cultured in the presence or absence of anti-leptin in vitro cuhure system containing of anti-CD3/CD28, and the percent of Tregs were detected by FACS on 40h and 80h. Results The leptin level in SLE patients was remarkably increased compared with healthy controls （P 〈 0.05）. The leptin levels in lupus moderate and severe active group were significantly higher than those of the healthy controls （ all P 〈 0.05 ）, and that in the lupus severe active group was definitely higher than the lupus moderate and mild group （ all P 〈 0.05）. The leptin level in SLE patients was positively correlated with SLEADI scores （ r = 0.316 2, P = 0. 030 4） but negatively correlated with Tregs in peripheral blood （ r = 0. 288 8, P = 0. 049 0） ; there was no correlation between leptin and Tregs in healthy control （r = 0. 121 9, P = 0. 561 5 ）. The Tregs expanded significantly after anti- leptin treatment in vitro culture system （P 〈 0.05 ）. Conclusion The level of serum leptin in SLE patients is higher than that of healthy control, and to some extent, the more severe the disease, the higher of leptin. Leptin may be involved in the pathogenesis of SLE by inhibiting inhibiting the proliferation of Tergs.