Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis

Abstract

Background and aim: Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC).

Material and methods: To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months.

Results: At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child).

Conclusion: The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

Figure 1

Granules of stainable iron (haemosiderin) within cytoplasm of epithelium of minor glands of the mucosa of the lower lip. Perls' technique with nuclear fast red counterstain, original magnification 1,000x.

Figure 2

Hepatectomy specimen, postnatal age 30 days. Nodularity is apparent. The relatively stroma-poor nodules consisted of hepatocellular parenchyma, sometimes cholestatic. The intervening regions that exhibit more compact connective-tissue elements were sites of hepatocellular loss and stromal collapse, with neocholangiolar transformation of remaining parenchyma. Reticulin, original magnification 40x.

Figure 3

Antigen specific anti-mitochondrial antibody (AMA) reactivity in the infant and his mother tested by ELISA. Optical density (y-axis) and time elapsed since birth of child (x-axis) are indicated.