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血清基质细胞衍生因子-1 升高对原发性胆汁性胆管炎的意义。

Implication of increased serum stromal cell-derived factor-1 for primary biliary cholangitis.

机构信息

Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, Taizhou, Zhejiang, China.

Department of Laboratory Diagnostics, Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

Int Immunopharmacol. 2018 Mar;56:285-290. doi: 10.1016/j.intimp.2018.01.046. Epub 2018 Feb 3.

DOI:10.1016/j.intimp.2018.01.046
PMID:29414663
Abstract

BACKGROUND

Stromal cell-derived factor-1 (SDF-1), also called chemokine (C-X-C motif) ligand 12 (CXCL12), as a chemokine for premature B cells, T cells and monocytes, is detected in liver, pancreas, spleen and heart. However, its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression is unclear. The aim of this study was to determine serum stromal cell-derived factor-1 (SDF-1) level and to explore its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression of PBC.

METHODS

A total of 60 PBC patients who received liver biopsy, 32 age- and sex-matched patients with chronic hepatitis B (CHB) and 30 age- and sex-matched healthy controls (HC) were recruited. The sera were measured for SDF-1, interleukin-4 (IL-4), interferon gamma (IFN-γ) and IL-17 using multiplex immunoassay. PBC was divided into four histologic stages according to Scheuer's classification.

RESULTS

The results showed significantly higher median level of serum SDF-1 (median, interquartile (IQR), 1186.96, 1002.05-1471.33 pg/mL) in PBC patients than those with CHB (median, IQR, 740.69,600.30-1239.27 pg/mL) and HC (median, IQR, 738.44, 687.65-879.33 pg/mL) (P < 0.001). There was no significant difference between CHB patients and HC (P = 0.526). The receiver operating characteristic curves (ROC) showed good diagnostic performance of serum SDF-1 for PBC, AMA-positive and -negative PBC. In particular for AMA-negative PBC, the area under ROC was 0.817, with optimal cutoff value of 802.64 pg/mL and the sensitivity of 100%. Serum SDF-1 level was not associated with other immune, inflammatory and fibrotic indicators, including AMA, ANA, anti-gp210, sp100 and centromere antibodies, bilirubin, ALT, AST, ALP, GGT, WBC, neutrophil, lymphocyte, platelet, Neutrophil- (NLR) and platelet-lymphocyte (PLR), AST to ALT ratio, AST to platelet ratio index (APRI) and FIB-4 index (P > 0.05). Also, there was no significant difference for serum SDF-1 among histological stages (P = 0.091). However, Serum SDF-1 level was significantly correlated with serum IL-17 (r = 0.373, P = 0.004), but not with IL-4 (r = 0.110, P = 0.407) and IFN-γ (r = 0.215, P = 0.098) in those with PBC.

CONCLUSION

Serum SDF-1 is increased in and may be a potential useful marker for PBC. Moreover, it may be associated with Th17 recruitment and differentiation in PBC. However, serum SDF-1 may not be associated with the progression of PBC.

摘要

背景

基质细胞衍生因子-1(SDF-1),也称为趋化因子(C-X-C 基序)配体 12(CXCL12),作为前 B 细胞、T 细胞和单核细胞的趋化因子,在肝脏、胰腺、脾脏和心脏中被检测到。然而,其对原发性胆汁性胆管炎(PBC)的诊断价值以及 SDF-1 与炎症和纤维化进展的关联尚不清楚。本研究旨在确定血清基质细胞衍生因子-1(SDF-1)水平,并探讨其对原发性胆汁性胆管炎(PBC)的诊断价值,以及 SDF-1 与 PBC 的炎症和纤维化进展的关联。

方法

共纳入 60 例接受肝活检的 PBC 患者、32 例年龄和性别匹配的慢性乙型肝炎(CHB)患者和 30 例年龄和性别匹配的健康对照(HC)。采用多重免疫测定法检测血清 SDF-1、白细胞介素-4(IL-4)、干扰素γ(IFN-γ)和 IL-17。根据 Scheuer 分类,将 PBC 分为四个组织学阶段。

结果

结果显示,与 CHB 患者(中位数,IQR,740.69,600.30-1239.27pg/mL)和 HC(中位数,IQR,738.44,687.65-879.33pg/mL)相比,PBC 患者血清 SDF-1 水平明显更高(中位数,IQR,1186.96,1002.05-1471.33pg/mL)(P<0.001)。CHB 患者与 HC 之间无显著差异(P=0.526)。受试者工作特征曲线(ROC)显示血清 SDF-1 对 PBC、AMA 阳性和阴性 PBC 的诊断性能良好。特别是对于 AMA 阴性 PBC,ROC 的曲线下面积为 0.817,最佳截断值为 802.64pg/mL,灵敏度为 100%。血清 SDF-1 水平与其他免疫、炎症和纤维化指标,包括 AMA、ANA、抗 gp210、sp100 和着丝粒抗体、胆红素、ALT、AST、ALP、GGT、白细胞、中性粒细胞、淋巴细胞、血小板、中性粒细胞-(NLR)和血小板-淋巴细胞(PLR)、AST 与 ALT 比值、AST 与血小板比值指数(APRI)和 FIB-4 指数(P>0.05)均无相关性。此外,血清 SDF-1 在组织学阶段之间无显著差异(P=0.091)。然而,血清 SDF-1 水平与血清 IL-17 显著相关(r=0.373,P=0.004),但与 IL-4(r=0.110,P=0.407)和 IFN-γ(r=0.215,P=0.098)无显著相关。

结论

血清 SDF-1 在 PBC 中增加,可能是 PBC 的一个潜在有用的标志物。此外,它可能与 PBC 中的 Th17 募集和分化有关。然而,血清 SDF-1 可能与 PBC 的进展无关。

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