Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum anti-mitochondrial Ab and lymphocyte-mediated bile duct damage. This study was designed to reveal the clonal characteristics of B lymphocyte repertoire in patients with PBC to facilitate better understanding of its pathogenesis and better management of these patients. Using high-throughput sequencing of Ig genes, we analyzed the repertoire of circulating B lymphocytes in 43 patients with PBC, and 34 age- and gender-matched healthy controls. Compared with healthy controls, PBC patients showed 1) a gain of 14 new clones and a loss of 8 clones; 2) a significant clonal expansion and increased relative IgM abundance, which corresponded with the elevated serum IgM level; 3) a significant reduction of clonal diversity and somatic hypermutations in class-switched sequences, which suggested a general immunocompromised status; 4) the reduction of clonal diversity and enhancement of clonal expansion were more obvious at the cirrhotic stage; and 5) treatment with ursodeoxycholic acid could increase the clonal diversity and reduce clonal expansion of the IgM repertoire, with no obvious effect on the somatic hypermutation level. Our data suggest that PBC is a complex autoimmune disease process with evidence of B lymphocyte clonal gains and losses, Ag-dependent ogligoclonal expansion, and a generally compromised immune reserve. This new insight into the pathogenesis of PBC opens up the prospect of studying disease-relevant B cells to better diagnose and treat this devastating disease.

[Investigate circulating levels of chemokines and evaluate the correlation between these chemokines and liver function indicators in autoimmune hepatitis].

OBJECTIVE: This study investigated circulation levels of chemokines (CCL2, CCL5, CXCL8, CXCL9, CXCL10) in autoimmune hepatitis(AIH) patients and evaluated the correlation between these chemokines and liver function indicators. METHODS: A total of 5 chemokines (CCL2, CCL5, CXCL8, CXCL9, CXCL10) were measured simultaneously by cytokine beads assay(CBA) in the sera of 46 patients with AIH and 12 cases of healthy control. RESULTS: In this study we found that serum levels of CCL2 , CXCL9 and CXCL10 in AIH patients and healthy controls were 11.79:8.39 pg/ml, 11.31:2.69 pg/ml, 15.85:4.64 pg/ml, respectively , which implied these chemokines were significantly higher in AIH patients when compared to healthy control (Z=-1.958, P=0.05; Z=-4.527, P less than 0.0001; Z=-3.84, P less than 0.0001, respectively). And circulation levels of CCL2 , CXCL8 , CXCL9 and CXCL10 in pretreatment and remission stages of patients with AIH were 29.69:11.16 pg/ml, 7.2:5.38 pg/ml, 16.02:5.47 pg/ml, 90.01:13.24 pg/ml, respectively, which showed these chemokines decreased during remission from pretreatment stage levels (t=2.985, P=0.005; Z=-2.547, P=0.0112; Z=-3.187, P=0.001; t=2.12, P=0.0015, respectively). Among AIH , CXCL8 was correlated positively with lgG(r2=0.291, P=0.0039); CXCL9 was associated positively with ALT and AST(r2=0.5324 , P less than 0.0001; r2=0.3352, P less than 0.0001); CXCL10 showed a positive correlation with ALT , AST and GGT(r2=0.9551, P less than 0.0001; r2=0.8960, P less than 0.0001; r2=0.8271, P less than 0.0001). CONCLUSION: Serum levels of CCL2, CXCL8, CXCL9 and CXCL10 are significantly higher in patients with AIH, but decrease to levels in healthy controls after successful treatment , and circulation levels of CXCL9 and CXCL10 are associated positively with liver function indicators which can react inflammation activity of liver, all these may imply that chemokines can reflect the degree of liver inflammation and may be one of the main culprits in AIH pathological damage.