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

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.