关键词: JIA PD1 pathway biomarkers immune checkpoint

来  源:   DOI:10.31138/mjr.140523.aso   PDF(Pubmed)

Abstract:
UNASSIGNED: To investigate the immunoregulatory role of the Programmed-cell-Death-protein-1 (PD1) pathway, an inhibitory immune checkpoint, in Juvenile Idiopathic Arthritis (JIA).
UNASSIGNED: The PD1 expression on CD4+ and CD8+ T-cells was determined by flow cytometry and the PD1 soluble form (sPD1) levels by ELISA, in peripheral blood (PB)/serum and synovial fluid (SF) samples of JIA patients and healthy controls (HCs). We searched for any association in-between the biomarkers and with JIA activity.
UNASSIGNED: 101 Caucasian patients (69 female), aged 12 (8-15) years, and 20 HCs participated in this study. The PB PD1 expression on T-cells was higher in: a. JIA patients vs HCs (CD4: 1.24% vs 0.32%, p=0.007, CD8: 1.6% vs 0.4%, p=0.002). b. active vs inactive JIA (CD4: 1.44% vs 0.87%, p=0.072, CD8: 2.1% vs 0.93%, p=0.005). The SF PD1 expression on T-cells correlated strongly and positively with the disease activity (CD4: ρ=0.55, p=0.022, CD8: ρ=0.555, p=0.026). The SF PD1 expression on CD8 T-cells was higher in patients on-treatment vs those off-treatment (21.3% vs 5.83% p=0.004). The sPD1 levels were higher in the SF vs the serum (801pg/ml vs 367.2, p=0.013), without an association with disease activity.
UNASSIGNED: These results indicate an up-regulation of the PD1-pathway in JIA, at least quantitatively, especially in active disease. sPD1 is compartmentally produced at the inflamed joints. Further investigation in a larger sample of JIA patients may verify these observations and contribute to unravelling the precise role of the PD1 pathway in the pathogenesis and persistence of the joint inflammation.
摘要:
为了研究程序性细胞死亡蛋白1(PD1)途径的免疫调节作用,抑制性免疫检查点,幼年特发性关节炎(JIA)。
通过流式细胞术确定CD4和CD8T细胞上的PD1表达,通过ELISA确定PD1可溶形式(sPD1)水平,在JIA患者和健康对照(HCs)的外周血(PB)/血清和滑液(SF)样本中。我们搜索了生物标志物与JIA活性之间的任何关联。
101名白种人患者(69名女性),12(8-15)岁,20个HCs参与了这项研究。在T细胞上的PBPD1表达在:a。JIA患者vsHCs(CD4:1.24%vs0.32%,p=0.007,CD8:1.6%vs0.4%,p=0.002)。B.活跃与不活跃的JIA(CD4:1.44%vs0.87%,p=0.072,CD8:2.1%vs0.93%,p=0.005)。T细胞上的SFPD1表达与疾病活动密切相关且呈正相关(CD4:ρ=0.55,p=0.022,CD8:ρ=0.555,p=0.026)。在治疗中的患者中,CD8T细胞上的SFPD1表达高于未治疗的患者(21.3%vs5.83%p=0.004)。sPD1水平在SF高于血清(801pg/mlvs367.2,p=0.013),与疾病活动无关。
这些结果表明JIA中PD1途径的上调,至少在数量上,特别是在活动性疾病中。sPD1在发炎的关节处间隔产生。在较大的JIA患者样本中进行的进一步研究可能会验证这些观察结果,并有助于揭示PD1途径在关节炎症的发病机理和持久性中的确切作用。
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