Allo-immunisation fœto-maternelle anti-CD10

Abstract

Les glomérulopathies (GEM) anténatales par allo-immunisation foeto-maternelle forment une nouvelle entité résultant du passage transplacentaire d’anticorps maternels qui se fixent sur les podocytes des glomérules fœtaux et induisent une maladie rénale. Les anticorps pathogènes sont dirigés contre l’endopeptidase neutre (EPN) qui est identique à l’antigène CD10. Les mères sont génétiquement déficientes en EPN et s’immunisent dès la première grossesse contre l’EPN/ CD10 présente sur les cellules placentaires. Cette maladie représente la première cause prouvée de pathologie d’organe induite par allo-immunisation fœto-maternelle. Les futures grossesses chez les mères immunisées étant à haut risque pour le foetus, il est impératif de mettre au point le dosage des anticorps anti-EPN/CD10, et des stratégies thérapeutiques visant à induire une tolérance spécifique.

Fetomaternal alloimmunization with antenatal glomerulopathies (FMAIG) is a recently described alloimmune disorder, which results from the production of maternal antibodies that cross the placenta, bind to fetal glomerular podocytes, and mediate renal disease. The pathogenic antibodies are directed against CD10/ neutral endopeptidase (NEP). The infant’s mother is NEP-deficient and thus she becomes immunized during the first pregnancy against CD10/NEP expressed by placental cells. Because future pregnancies in CD10/ NEP-immunized mothers are at high risk for the fetus, detection of anti-NEP antibodies in pregnant mothers and antigen-driven therapies including induction of tolerance, are urgently needed. This ideally requires identification of the pathogenic epitopes born by the antigen and specifically recogninized by B- and T-cells. We have recently characterized such epitopes that will be used in diagnostic tests (ELISA) and for new therapeutic approaches based on peptide-specific immune intervention. For this purpose, we have developed an experimental model by crossing NEP/CD10-deficient female mice to wild-type males. The females develop an alloimmune reaction against NEP, which is a prerequisite for tolerance induction experiments. Although NEP/CD10 does not seem to be involved in common idiopathic forms of membranous nephropathy in the adult, alloimmune antibodies may be implicated in de novo membranous nephropathy that develop in the kidney graft and after alloimmune bone marrow transplantation.