Introduction Two childhood autoimmune liver diseases are recognised: “classical” autoimmune hepatitis (AIH) and AIH-sclerosing cholangitis overlap syndrome (also termed as autoimmune sclerosing cholangitis, ASC). ASC is characterised by ANA and/or SMA seropositivity, hypergammaglobulinaemia and interface hepatitis—all features typical of “classical” AIH—in conjunction with bile duct destruction. Previous studies showed that regulatory T-cells, a subset essential for immune-tolerance maintenance, are defective in both conditions. Whether different CD4 and CD8 effector T-cell responses account for the clinical spectrum of childhood autoimmune liver disease is unknown. Aims: to evaluate the frequency and phenotype of CD4 and CD8 T-cells in patients with AIH and ASC.

Methods 6 patients with AIH, six patients with ASC, and six healthy subjects (HS) were studied. The frequency and phenotype of T-cells was evaluated by cytofluorimetry using monoclonal antibodies against CD3, CD4 and CD8. Expression of T-bet, RORC, IFN-g and IL-17 was determined by intracellular staining.

Results The frequency of CD4^poscells within total lymphocytes was lower in ASC (36.5±3.6), compared to AIH (47.2±2.7, p=0.04) and HS (46.8±2.1, p=0.04). Conversely, ASC patients displayed higher percentage of CD8^poscells (31.8±2) than in AIH (21.8±2.5, p=0.01) and HS (22.9±1.3, p=0.03), therefore exhibiting a lower CD4:CD8 compared to AIH and HS. Within CD4^posT-cells: (a) T-bet^pos and IFN-g^poscells were higher both in AIH and ASC compared to HS (T-bet: p=0.01 for AIH, p=0.05 for ASC; IFN-g: p=0.02 for AIH, p=0.03 for ASC); (b) RORC^pos and IL-17^poscells were more frequent in ASC than in AIH (RORC: p=0.001; IL-17: p=0.02). Within CD8-T cells: (a) IFN-g-producing cells were higher in AIH and ASC than HS (p=0.004 for AIH, p=0.08 for ASC); b) IL-17-producing cells were higher in ASC compared to AIH (p=0.05). In ASC, frequency of CD4^pos and CD8^posIL-17^poscells correlated with γ-glutamyl-transpeptidase (R=0.90, p=0.01 for CD4; R=0.84, p=0.04 for CD8), and with alkaline phosphatase levels (R=0.75, p=0.09 for CD4; R=0.80, p=0.06 for CD8).

Conclusion Both AIH and ASC are associated with an increase of IFN-g-producing cells. Compared to AIH, ASC patients have more CD8 T-cells, and higher number of IL-17-producing T-cells. The correlation with cholestatic biochemical abnormalities suggests that IL-17 is involved in bile duct involvement characteristic of ASC.

Competing interests None declared.