Although chemokines have been believed to exert a pivotal role in pathogenesis of primary biliary cholangitis (PBC), comprehensive analysis of circulating chemokine profile in PBC has been little performed. The aim of this study is to determine serum chemokine profile and to explore its association with the development and progression of PBC. Sixty PBC patients and 30 healthy controls (HC) were enrolled. The sera were detected for 14 chemokines using multiplex immunoassay. The expression of CD3 and CD68 in the portal area of liver tissues was determined by immunohistochemistry in 6 PBC patients. The characteristics of chemokine profile in PBC were analyzed. Serum concentrations of most chemokines were higher, but TARC/CCL17, MDC/CCL22 and ENA-78/CXCL5 were lower in PBC patients than those in HC (all P < 0.05). Most of increased chemokines remained significant in both early and advanced PBC patients. PBC stage was correlated inversely with MCP-4/CCL13(r = -0.373), TARC/CCL17(r = -0.365), ENA-78/CXCL5 (r = -0.418) and I-TAC/CXCL11(r = -0.262), but positively with fractalkine/CX3CL1(r = 0.325). There were significant correlations between serum levels of IP-10/CXCL10 (r = 0.971, P = 0.001) and I-TAC/CXCL11 (r = 0.883, P = 0.020) and CD3 expression within the portal area, and between MIP-3α/CCL20 and CD68 expression within the portal area (r = 0.886, P = 0.019). In PBC patients, there were significant correlations among each other of MCP-4/CCL13, TARC/CCL17, MDC/CCL22, CTACK/CCL27, ENA-78/CXCL5, IP-10/CXCL10, I-TAC/CXCL11, excepting correlations of CTACK/CCL27 with IP-10/CXCL10 and I-TAC/CXCL11. Also, there were strong correlations among each other of CCL3/MIP-1α, CCL4/MIP-1β and IL-8/CXCL8. The only negative correlation was found in the serum between fractalkine/CX3CL1 and TARC/CCL17 (r = -0.311, P = 0.016). Serum levels of most chemokines are increasing throughout the development and progression of PBC, with the exception of chemokines, mainly attractive for neutrophil and eosinophil (e.g. ENA-78/CXCL5, MCP-4/CCL13), decreasing in advanced PBC, and of chemokines, dominantly responsible for Th2 chemotaxis (e.g. TARC/CCL17), decreasing in early PBC and associating negatively with PBC progression.

中文翻译：

---

原发性胆汁性胆管炎血清趋化因子谱的特征

尽管人们认为趋化因子在原发性胆汁性胆管炎 (PBC) 的发病机制中发挥着关键作用，但对 PBC 中循环趋化因子谱的综合分析却很少进行。本研究的目的是确定血清趋化因子谱并探讨其与 PBC 发生和进展的关联。招募了 60 名 PBC 患者和 30 名健康对照 (HC)。使用多重免疫测定法检测血清中的 14 种趋化因子。免疫组化检测 6 例 PBC 患者肝组织汇管区 CD3 和 CD68 的表达。分析了PBC趋化因子谱的特征。大多数趋化因子的血清浓度较高，但 PBC 患者的 TARC/CCL17、MDC/CCL22 和 ENA-78/CXCL5 低于 HC（均 P < 0.05）。大多数增加的趋化因子在早期和晚期 PBC 患者中仍然显着。PBC 分期与 MCP-4/CCL13(r = -0.373)、TARC/CCL17(r = -0.365)、ENA-78/CXCL5 (r = -0.418) 和 I-TAC/CXCL11(r = -0.262) 呈负相关)，但与 fractalkine/CX3CL1(r = 0.325) 相关。IP-10/CXCL10（r = 0.971，P = 0.001）和I-TAC/CXCL11（r = 0.883，P = 0.020）的血清水平与汇管区内CD3表达之间以及MIP-3α之间存在显着相关性/CCL20 和 CD68 在汇管区内的表达 (r = 0.886, P = 0.019)。在PBC患者中，除相关外，MCP-4/CCL13、TARC/CCL17、MDC/CCL22、CTACK/CCL27、ENA-78/CXCL5、IP-10/CXCL10、I-TAC/CXCL11之间存在显着相关性CTACK/CCL27 与 IP-10/CXCL10 和 I-TAC/CXCL11。还，CCL3/MIP-1α、CCL4/MIP-1β和IL-8/CXCL8之间存在很强的相关性。在 fractalkine/CX3CL1 和 TARC/CCL17 之间的血清中发现唯一的负相关（r = -0.311，P = 0.016）。大多数趋化因子的血清水平在 PBC 的整个发展和进展过程中都在增加，但趋化因子除外，主要对中性粒细胞和嗜酸性粒细胞（例如 ENA-78/CXCL5、MCP-4/CCL13）有吸引力，在晚期 PBC 和趋化因子中降低，主要负责 Th2 趋化性（例如 TARC/CCL17），在早期 PBC 中减少并与 PBC 进展呈负相关。