What this Trial Is About

IgA nephropathy (IgA Nephropathy), or Berger's disease, is the most common form of primary glomerulonephritis. It is a major cause of end-stage renal failure, often leading to dialysis or kidney transplantation. Recurrence is common after transplantation, compromising graft survival. Rheumatoid purpura (or IgA vasculitis) shares a common pathophysiology with IgA N, characterised by mesangial deposits containing IgA-rich immune complexes, but differs in its systemic involvement (skin, joints and digestive system). In terms of pathophysiology, the histological signature of these conditions is based on the accumulation of abnormal IgA within the glomerulus. The mechanisms responsible for the nephrotoxicity of these IgA remain partially unclear. In patients with NIgA, several qualitative abnormalities of IgA have been well described, including a glycosylation defect that promotes IgA polymerisation and the emergence of anti-IgA autoantibodies. These immune complexes, found in glomerular deposits, induce a local inflammatory reaction. Experimental work conducted on mouse models developed at the CRIBL laboratory has shown that these abnormalities may be linked to a dysregulation of the immune response, leading to the production of IgA with physicochemical properties that promote their deposition in the kidney. However, the location of nephritogenic IgA-secreting B cells remains poorly understood. Recent data suggest that this production could occur directly within the renal parenchyma, where activated B lymphocytes would locally produce pathogenic IgA. Following on from these observations, our study aims to characterise the immunoglobulin (Ig) repertoires in patients with IgA nephropathy, particularly those from renal lymphoid infiltrates, and to compare them with the repertoires of circulating B cells. We hypothesise that certain sequence motifs within the variable domains of IgA, particularly the CDR3 regions, could constitute specific biomarkers of NIgA. Their detection in peripheral blood could enable non-invasive or predictive diagnosis, complementing the renal biopsy that is currently essential.

Identification and Characterisation of IgA With Nephritogenic Potential in IgA Deposition Nephropathies (Rep-IgAN)