关键词: 银屑病, CD4阳性T淋巴细胞, 干扰素γ, 白细胞介素17, 前蛋白转化酶枯草溶菌素9

Abstract: 【Abstract】 Objective To investigate the role of proprotein convertase subtilisin/kexin type 9 （PCSK9） in the pathogenesis of psoriasis by detecting the level of PCSK9 in the plasma of patients with psoriasis and evaluating its effect on the secretion of interferon gamma （IFN-γ） and interleukin-17A （IL-17A） by peripheral CD4+ T cells. Methods Totally, 30 outpatients with psoriasis vulgaris and 30 healthy volunteers （controls） were enrolled from Hospital for Skin Diseases, Chinese Academy of Medical Sciences between February 2016 and December 2017. Of the 30 patients, 16 were males, and 14 were females. Their age varied from 18 to 66 years, and the course of disease ranged from 1 month to 15 years. Peripheral venous blood samples were obtained from the patients and controls, and the plasma and peripheral blood mononuclear cells （PBMC） were isolated. Real-time fluorescence-based PCR （q-PCR） was performed to measure mRNA expression of PCSK9 in the PBMC, and enzyme-linked immunosorbent assay （ELISA） to determine the concentration of PCSK9 in the plasma. Peripheral CD4+ T cells were isolated from the PBMC by magnetic bead method, and divided into 2 groups to be co-cultured with （experiment group） or without PCSK9 protein （control group）. After 24-hour treatment, ELISA was conducted to detect the levels of IFN-γ and IL-17A in the culture supernatant. Statistical analysis was carried out by using two-sample t test for the comparison between the two groups, and Pearson correlation analysis for analyzing correlations between the plasma level of PCSK9 and psoriasis area and severity index （PASI） score in the patients with psoriasis. Results PCSK9 mRNA expression was undetected in the PBMC of the patients with psoriasis and controls. The plasma level of PCSK9 was significantly higher in the patients with psoriasis （［243.58 ± 11.91］μg/L） than in the healthy controls （［199.74 ± 31.09］μg/L, t = 5.761, P < 0.001）. After co-culture of the peripheral CD4+ T cells from patients with PCSK9 protein, the levels of IFN-γ and IL-17A both significantly increased （［6 150.00 ± 212.13］ ng/L, ［1 532.00 ± 11.31］ ng/L, respectively） compared with the control group co-cultured without PCSK9 protein （［4 650.00 ± 212.13］ ng/L, ［698.5 ± 266.58］ ng/L, respectively; t = 7.071, 4.418 respectively, both P < 0.05）. IFN-γ and IL-17A were undetected in the culture supernatant of CD4+ T cells from the healthy controls in the experiment group or control group. Conclusion The plasma level of PCSK9 increases in patients with psoriasis, which may be involved in the pathogenesis of psoriasis by activating peripheral CD4+ T cells.

Key words: Psoriasis, CD4?positive T?lymphocytes, Interferon?gamma, Interleukin?17, Proprotein convertase subtilisin/kexin type 9