ABSTRACT Aim To identify autoimmune hepatitis (AIH)‐specific autoantibodies using a high‐content human protein microarray and evaluate their diagnostic performance. Methods Pretreatment sera from untreated patients with AIH ( n = 68), primary biliary cholangitis (PBC, n = 19), metabolic dysfunction‐associated steatotic liver disease (MASLD, n = 39), chronic hepatitis C (CHC, n = 27), and drug‐induced liver injury (DILI, n = 18) and healthy controls (HC, n = 37) were screened with a wheat‐germ, cell‐free microarray displaying > 16,000 proteins. Candidate antigens were validated by ELISA, and antibody titers were correlated with clinical variables, treatment response, and outcomes. Results Mitochondrial ribosomal protein S27 (MRPS27) emerged as the dominant AIH‐associated antigen. The mean anti‐MRPS27 antibody titer in untreated patients with AIH (50.2 AU) exceeded that in patients with PBC (9.3 AU), MASLD (12.8 AU), CHC (24.8 AU), DILI (19.8 AU), and HC (7.5 AU, all p < 0.01). A cutoff of 35.4 AU (HC mean + 2 SD) yielded a sensitivity of 61.8%, a specificity of 87.1%, a positive predictive value of 70.0%, and a negative predictive value of 82.4%. Positivity was unrelated to baseline histology, biochemistry or IgG, and titers were unchanged after corticosteroid induction. Interestingly, patients with low titers experienced more liver‐related events during follow‐up. Conclusion The anti‐MRPS27 antibody is a promising adjunctive serological marker that enhances the specificity of AIH diagnosis. The pathogenic significance and prognostic value of this antibody warrant prospective validation.
Wada et al. (2026) studied this question.