A new mouse model of anti-GBM disease sheds light on maternal transfer of alloantibodies in glomerular disease (1)
In Membranous nephropathy (MN), the two main antigens that are recognized by autoantibodies are the M-type phospholipase A2 receptor (70%–80% of cases) and thrombospondin type 1 domain-containing 7A (3%–5% of cases). The prevalent IgG subclass is IgG4 which weakly binds complement.
In anti-GBM disease, the antigen recognized by autoantibodies is in the vast majority of patients the noncollagenous domain 1 of the a3 chain of type IV collagen, also known as the “Goodpasture (auto)antigen.” The predominant IgG subclasses are IgG1 and IgG3, which can activate the complement pathway,
For MN, the classical Heymann nephritis model in rats and several models of anti-GBM nephropathy developed in sheep, rats, or transgenic mice. In these models, the antigenicity of autoantigens is usually elicited by adding Freund’s adjuvant. In addition, disease can be induced by passive transfer after injecting heterologous antisera, demonstrating the pathogenicity of these antibodies.
In a maternal transfer of immunoglobulins causing glomerular disease, the best characterized model is neonatal alloimmunization by passive transfer of anti-neutral endopeptidase protein (NEP) antibodies, causing neonatal MN. The subclass of IgG may play a role, as suggested by more severe disease in a newborn with MN secondary to anti-NEP antibodies of the IgG1 subclass, which activated the complement pathway and inhibited NEP enzymatic activity.
