Taubert R, Engel B, Diestelhorst J, et al. - Polyreactive IgG (pIgG) has the potential to be a novel promising marker for improving the diagnostic workup of liver diseases, with a higher specificity for autoimmune hepatitis (AIH) than conventional autoantibodies and value in autoantibody negative AIH. Similarly, in untreated AIH, pIgG could be a major cause of assay interference.

• IgG antibodies with a binding capacity to many human and foreign proteins were found with a protein macro-array and verified with solid-phase ELISAs in AIH patients during the search for more precise autoantibodies to identify AIH from non-AIH liver disorders.

• Following that, pIgG was quantified using a reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA).

• The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was evaluated in cryo-conserved samples from 1,568 adults from ten centers in eight countries in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort.

• HIP1R/BSA reactivity had a 25% and 14% higher specificity for diagnosing AIH than conventional anti-nuclear and anti-smooth muscle antibodies, a significantly higher sensitivity than liver-kidney microsomal antibodies and anti-soluble liver antigen/liver pancreas antigen, and a 12-20% higher accuracy than conventional autoantibodies.

• HIP1R/BSA reactivity was found in up to 88 % of seronegative AIH patients and up to 71% of AIH patients with normal IgG levels.

• Under therapy, pIgG levels in non-AIH liver diseases return to normal.