New insights in the pathogenesis of IgA nephropathy.
IgA nephropathy (N) or Berger's disease is the most common form of primary glomerulonephritis worldwide and one of the first cause of end-stage renal failure. The disease is characterized by the accumulation in mesangial areas of complexes containing polymeric IgA1. The mechanisms involved in the pathogenesis of IgAN is only now emerging. We discussed here three essential points: (i) the generation of abnormal IgA1 and formation of IgA1 complexes; (ii) the generation of mesangial injury mediated by interaction of IgA1 complexes with mesangial IgA1 receptors, and (iii) the progression of IgA-mediated mesangial injury towards renal failure. In summary, our data reveal that quantitative and structural changes of IgA1 play a key role on the onset of the disease due to functional abnormalities of two IgA receptors: the Fc alphaRI (CD89) expressed by blood myeloid cells and the transferrin receptor (CD71) on mesangial cells. Abnormal IgA induces release of soluble CD89 soluble leading to the formation of circulating IgA complexes, which in turn may be trapped by CD71 that is overexpressed on mesangial cells in IgAN patients allowing formation of IgA1 deposits. The elucidation of IgA-receptor interactions may open new avenues for drug design and treatment of IgAN.
Monteiro
R C
RC
INSERM U699, Bichat Medical School, 16 Rue Henri Huchard BP416, 75870 Paris, France. monteiro@bichat.inserm.fr
D000936:Antigen-Antibody Complex / Q000276:immunology; D018450:Disease Progression; D005920:Glomerular Mesangium / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000209:etiology; D011961:Receptors, Fc / Q000276:immunology; D013997:Time Factors
D000936:Antigen-Antibody Complex; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc