细胞因子与原发性胆汁性胆管炎疾病活动性及熊脱氧胆酸治疗应答的关联性
Research on the association of cytokines with disease activity and ursodeoxycholic acid treatment response in patients with primary biliary cholangitis
摘要目的:检测原发性胆汁性胆管炎(PBC)患者血浆12种细胞因子的表达水平,探讨细胞因子在PBC中的表达及其与PBC患者疾病活动情况和熊脱氧胆酸(UDCA)治疗效果的关联性。方法:回顾性横断面研究。选取2021年12月至2023年11月在北京协和医院就诊的127例PBC患者(PBC组)以及同期进行体检的32名健康志愿者作为健康对照组。通过流式细胞术检测其血浆12种细胞因子的表达情况,比较各组间细胞因子表达水平的差异,利用Spearman分析评价细胞因子水平与5种反映PBC疾病活动性实验室检查指标[包括碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBil)、天冬氨酸转氨酶(AST)、总胆汁酸(TBA)]的相关性,采用受试者工作特征(ROC)曲线评价细胞因子鉴别UDCA治疗应答与治疗不应答PBC患者的效能。结果:PBC组血浆白细胞介素(IL)-8水平与健康对照组比较,差异无统计学意义( P>0.05),PBC组血浆干扰素(IFN)-γ水平高于健康对照组( P<0.05)。Spearman分析显示,IL-8与ALP、GGT、TBil、AST、TBA均呈正相关( R2=0.348、0.401、0.406、0.495、0.417; P均<0.01),IFN-γ与ALP、GGT及TBA水平呈负相关( R2=-0.265、-0.253、-0.232; P均<0.05)。UDCA治疗不应答PBC患者( n=52)血浆IL-8水平高于UDCA治疗应答PBC患者( n=56)( P<0.05),而IFN-γ水平低于UDCA治疗应答PBC患者( P<0.05)。ROC曲线分析显示,血浆IL-8与IFN-γ区分UDCA治疗应答与不应答PBC患者的曲线下面积分别为0.631、0.783,敏感度分别为87.5%、90.5%,特异度分别为44.2%、57.9%。 结论:血浆IL-8与IFN-γ水平与PBC疾病活动情况具有一定的相关性,且可用于反映PBC患者UDCA的治疗效果。
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abstractsObjective:To detect the expression levels of 12 cytokines in the plasma of patients with primary biliary cholangitis (PBC) and explore their association with PBC disease activity and ursodeoxycholic acid (UDCA) therapeutic response.Methods:This study enrolled 127 patients with PBC who visited Peking Union Medical College Hospital between December 2021 and November 2023 (PBC group) and 32 healthy controls who underwent physical examinations during the same period (control group). The expression of 12 cytokines was measured using flow cytometry, and compared between groups. Spearman correlation analysis was performed to assess the relationship between cytokine levels and five laboratory indicators reflecting PBC disease activity [alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBil), aspartate aminotransferase (AST), and total bile acid (TBA)]. Furthermore, the receiver operating characteristic (ROC) curve analysis was performed to evaluate the effectiveness of cytokines in distinguishing between patients who responded to UDCA treatment and those who did not.Results:The plasma interleukin (IL)-8 levels between the PBC group and healthy controls showed no significant differences, and the plasma IFN-γ levels in PBC patients were significantly higher than those in health controls ( P<0.05). Spearman analysis showed that IL-8 was positively correlated with ALP, GGT, TBil, AST, and TBA ( R2=0.348, 0.401, 0.406, 0.495, 0.417; all P<0.01), and negative correlation was observed between IFN-γand ALP, GGT, and TBA levels ( R2=-0.265, -0.253, -0.232; all P<0.05). The plasma IL-8 level in 52 PBC patients who did not respond to UDCA treatment was significantly higher, while the IFN-γ level was significantly lower than those in 56 PBC patients who responded to UDCA treatment (both P<0.05). ROC analysis showed that the area under the curve for distinguishing plasma IL-8 and IFN-γlevels between PBC patients responding to UDCA treatment and not is 0.631 and 0.783, respectively. The sensitivities were 87.5% and 90.5%, and the specificities were 44.2% and 57.9%, respectively. Conclusion:The levels of plasma IL-8 and IFN-γ are correlated with the disease activity of PBC and can be used to reflect the therapeutic responses to UDCA in PBC patients.
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