Table 1 Features of antenatal membranous glomerulonephritis (AMG) and neonatal hemochromatosis (NH) in support or against alloimmunity

Organ specific?

Yes: Renal

Yes: Fetal Liver

Antigen identified?

Yes: Neutral endopeptidase (NEP). Subsequent maternal production of anti-NEP antibodies

Unidentified: Believed to be isolated to the fetal liver. Some report an antigen in the 32 kDa range

IgG present in affected organ?

Yes: IgG1, 3, 4 identified but IgG1 and 3 appear to be pathogenic; IgG4 associated with subclinical disease. IgG colocalised with the antigen

Yes: IgG identified on hepatocytes

Membrane attack complex (MAC) demonstrated in affected organ?

Yes: Heavy C5b-9 staining colocalised with the NEP antigen and IgG

Yes: Increased C5b-9 on hepatocytes of NH patients.

Intravenous immunoglobulin (IVIG) treatment successful?

Yes: IVIG treatment reduces the maternal titers of anti-NEP antibodies

Yes: IVIG treatment in mothers from the 18th week in subsequent pregnancies greatly reduces the disease severity and incidence

Animal models?

Yes: Rabbits injected with IgG from mothers with AMG affected children developed renal disease similar to AMG

Yes: Pregnant mice injected with IgG from mothers with NH affected children has increased rates of stillbirths, and fetus’ showed severe liver injury similar to that seen in NH

Aetiology of maternal immunisation identified?

Yes: Maternal defect in the Metallomembrane Endopeptidase (MME) gene, which encodes NEP

Unknown