重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对中重度银屑病患者血清脂肪因子水平的影响:前瞻性非随机对照试验

Effects of the Receptor-IgG Fc Fusion Protein of Recombinant Type Ⅱ Human Tumor Necrosis Factor-α on the Levels of Serum Adipokines in Psoriatic Patients:A Prospective Non-randomized Controlled Trial

目的分析注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对中重度斑块型银屑病患者血清脂联素(adiponectin,APN)、视黄醇结合蛋白4 (retinol binding protein 4,RBP4)、瘦素(leptin,LEP) 3种脂肪因子水平的影响。方法选取2016年11月至2018年5月在北京协和医院皮肤科就诊的30例中重度斑块型银屑病患者作为治疗组,同时选取在本院健康医学部进行体检的25名健康人作为健康对照组。治疗组均给予重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白50 mg皮下注射,每周1次,共12次。检测健康对照组及治疗组治疗前(基线)和治疗后12周血清APN、RBP4、LEP的浓度;分析两组之间以及治疗组治疗前后血清脂肪因子水平是否存在差异,并采用Spearman相关分析法评估治疗组基线血清APN、RBP4、LEP表达水平与银屑病皮损面积和严重程度指数(psoriasis area and severity index,PASI)之间有无线性相关关系。结果治疗组基线APN水平[9. 73(6. 69,12. 37)比(14. 25 (10. 53,23. 28),P <0. 001]、LEP水平[0. 42 (0. 17,2. 60)比3. 90 (1. 38,7. 20),P=0. 002]较健康对照组降低, RBP4较健康对照组升高[12. 29 (10. 62, 21. 33)比9. 13 (7. 36,15. 78),P=0. 024];治疗组治疗后APN水平[11. 95 (8. 12,15. 26)比9. 73 (6. 69, 12. 37), P=0. 027]、LEP水平[2. 84 (1. 04,9. 34)比0. 42 (0. 17,2. 60),P<0. 001]较治疗前明显升高,而RBP4水平较治疗前差异无统计学意义(P=0. 125);基线APN、RBP4、LEP浓度均与PASI无线性相关关系。结论脂肪因子可能参与了银屑病的慢性炎症过程,抗肿瘤坏死因子α治疗可能改善银屑病的炎症状态。

ObjectiveTo analyze the effects of the receptor-IgG Fc fusion protein of recombinant type Ⅱ human tumor necrosis factor-α(TNF-α) on serum levels of adiponectin (APN), retinol binding protein 4(RBP4), and leptin (LEP) in patients with moderate to severe plaque psoriasis. MethodsA total of 30 patients with moderate to severe plaque psoriasis and 25 healthy volunteers were enrolled in the study. The psoriatic patients were subcutaneously injected with type Ⅱ human TNF-α receptor-IgG Fc fusion protein 50 mg once a week for 12 weeks. The serum levels of APN, RBP4, and LEP were assessed and compared before and after the treatment of 12 weeks, in psoriatic patients, as well as in the controls. Spearman correlation analysis was used to evaluate the linear correlations of baseline serum APN, RBP4, LEP levels with psoriasis area and severity index(PASI) in the treatment group. ResultsBefore the treatment, the levels of APN[9.73(6.69,12.37) vs. 14.25(10.53,23.28), P <0.001] and LEP[0.42(0.17,2.60) vs. 3.90(1.38,7.20), P =0.002] were lower, RBP4 was higher[12.29(10.62,21.33) vs. 9.13(7.36,15.78), P =0.024] in psoriatic patients than those in normal controls. After the treatment, the levels of APN[11.95(8.12,15.26) vs. 9.73(6.69,12.37), P =0.027] and LEP[2.84(1.04,9.34) vs. 0.42(0.17,2.60), P <0.001] in the psoriatic patients were markedly increased, while the level of RBP4 showed no significant change( P =0.125). There was no linear correlation of the levels of APN, RBP4, LEP with PASI in the baseline period. ConclusionsAPN, RBP4 and LEP are closely related to the chronic inflammatory state of psoriasis. Anti-TNF-α therapy may improve the metabolic state of patients with psoriasis.