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These findings significantly expand our understanding of the disease susceptibility and suggest IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation, are critical components in the development of PBC.

Notably, several recent studies have found increased production of IL21 from T follicular helper (Tfh) cells in PBC patients, which might mediate B-cell maturation and autoantibody secretion.The chromosomal distribution of all the P-values (−log10 P-values) is shown.=0.68) in the Han Chinese population, implying that the functional variation in the TNFSF15 promoter can affect the genetic susceptibility to PBC.IL12A was found to be strongly associated with Han Chinese PBC cohorts, in contrast to both the Japanese GWAS and our previous candidate gene study.These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC.Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic inflammation and destruction of intrahepatic bile ducts.

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