title: Mechanisms of disease: Alloimmunization in renal diseases.
abstract: Graft rejection has long been considered the paradigm of renal diseases induced by alloimmunization, particularly alloimmunization directed against HLA antigens. Accumulating evidence indicates that non-HLA immunity also has an important role in clinical transplantation. Targets of alloimmunization include antigens of tubular basement membrane, tubular epithelial cells and endothelial cells. They can be polymorphic allovariants (as shown in the rat) or 'hidden' antigens exposed when the graft is damaged. Alloimmunization can also occur when a person genetically deficient in a renal protein (e.g. the alpha5 (IV) collagen chain in X-linked Alport's syndrome or nephrin in Finnish-type nephrotic syndrome) is transplanted to treat end-stage renal failure. The non-mutated protein in the donor kidney is recognized as a foreign antigen, and the resulting alloimmune response can damage the graft. We have demonstrated that alloimmunity can also affect the native kidney. We have characterized a novel fetomaternal disease in which a genetic defect in the MME gene encoding neutral endopeptidase (NEP) in the mother leads to the development of membranous nephropathy in her fetus (maternal anti-NEP antibodies bind to NEP on fetal podocytes). Our findings raise the possibility that mutations or genetic polyporphisms in MME or other genes expressed by the podocyte are involved in alloimmune-mediated development of membranous nephropathy after kidney or bone marrow transplantation.
authors.affiliation: INSERM Unit 702, University Pierre and Marie Curie, Tenon Hospital, Paris, France. pierre.ronco@tnn.aphp.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.forename: Vincent
authors.initials: V
authors.lastname: Guigonis
mesh_terms: D006801:Humans; D007674:Kidney Diseases / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*