Background & aims: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations of both copies of the autoimmune regulator (AIRE) gene. It is characterized by susceptibility to mucocutaneous candidiasis and multiple autoimmune lesions. A serious disease component is hepatitis. To identify diagnostic autoantibodies for APECED hepatitis, sera from 64 patients with APECED were screened for autoantibodies established in the diagnosis of idiopathic autoimmune hepatitis, and for autoantibodies against 10 cytochrome P450s.
Methods: Screening methods were indirect immunofluorescence, Western blot, Ouchterlony gel diffusion, enzyme-linked immunosorbent assay, and immunoprecipitation.
Results: Anti-liver microsomal antibodies were detected in 50% of the patients with APECED hepatitis and 11% of those without hepatitis. Prevalences of antinuclear, smooth muscle, anti-liver cytosol, anti-soluble liver protein/liver pancreas, and anti-CYP2D6 autoantibodies were 9%, 6%, 3%, 0%, and 0%, respectively. CYP1A1, CYP2B6, CYP1A2, and CYP2A6 were identified as autoantigens. Thirty percent of patients with anti-CYP2A6 and 100% of patients with anti-CYP1A2 were affected by hepatitis. Despite the high specificity of anti-CYP1A2 for APECED hepatitis, its sensitivity was low (50%). Anti-CYP2A6 and anti-CYP1A2 were not detected in patients with autoimmune hepatitis (N = 68) or nonhepatitic controls (N = 81).
Conclusions: Anti-CYP1A2 is a highly specific but insensitive marker for APECED hepatitis. No clinical correlation was observed for anti-CYP2A6. Autoimmune hepatitis and APECED hepatitis are characterized by different molecular targets of autoantibodies with no overlap.