[Immunoglobulin A (IgA) and its cellular receptors: Recent advances and new pathogenetical hypothesis].
Researchers have always been focusing their interest on IgA nephropathy, a nephropathy named after a class of immunoglobulin, and on circulating IgA in these patients. However, serum level studies conducted on IgA and IgA containing immune complexes have not fulfilled the expectations of providing useful tools for diagnosis and prognosis of this renal disease. Over recent years interest has grown on qualitative properties of IgA, particularly IgA1, the mostly represented subclass in renal deposits. The sugar composition of the short carbohydrate chains characteristic of the IgA1 hinge region has been thoroughly investigated, and a defective glycosylation of serum IgA1 in IgAN patients was detected with increase in desialylated and degalactosylated carbohydrate chains, and exposure of internal N-acetylgalactosamine residues. These aberrantly glycosylated IgA1 have the properties of self-aggregation, auto-antibody enhancement with IgA1/IgG immunocomplexes formation, and activation of complement and nuclear transcription factors such as NF-kB. Among others, aberrantly glycosylated IgA1 react with FC RI receptor on peripheral lymphomonocytes and, after shedding, the complex is released in form of macromolecular IgA. At mesangial level the nephrotoxicity of aberrantly glycosylated IgA1 seems to be mediated by the transferrin receptor (TfR) binding, selectively expressed on mesangial cells. This report aims at reviewing the most recent knowledge on IgA synthesis alterations and the subsequent biological effects on the pathogenesis of this nephritis so widespread in Europe.
Amore
A
A
S C Nefrologia Dialisi Trapianto, Indirizzo di Nefrologia Pediatrica, Scuola di Pediatria, Universita' di Torino, Ospedale Regina Margherita, Torino-Italy.
Monteiro
R
R
Coppo
R
R
D018450:Disease Progression; D005922:Glomerulonephritis, IGA / Q000209:etiology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*
D007070:Immunoglobulin A; D011971:Receptors, Immunologic