Complementary use of autoantibody detection methods facilitates diagnosis of juvenile autoimmune hepatitis and autoimmune sclerosing cholangitis

Autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC) are rare paediatric liver diseases that can be difficult to distinguish from other hepatopathies. Autoantibody testing is central to diagnosis, yet paediatric performance across platforms has been poorly standardised and sparsely reported. In this multicentre comparison (202 sera from nine expert centres across eight European countries), indirect immunofluorescence (IFT) on rodent tissue showed suboptimal discrimination at the commonly advocated 1:20 cut-off, whereas accuracy for ANA and SMA improved markedly at 1:320. ANA detection by IFT on HEp-2 cells and by ELISA was comparable to rodent tissue IFT. ELISAs for F-actin and pIgG achieved the highest AUCs for identifying AIH/AISC and may complement current diagnostics. Substantial inter-platform discordance for ANA underscores the need for harmonisation. Collectively, these data support the use of multiple validated platforms with platform-appropriate cut-offs in paediatric AIH/AISC serology and support updates to diagnostic algorithms to improve diagnostic timeliness and reliability.