Immunopathogenesis of IgAN

Abstract

The defining hallmark of IgA nephropathy (IgAN) is deposition of polymeric IgA1 in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis. The mechanisms involved in mesangial polymeric IgA1 deposition and the initiation of inflammatory glomerular injury remain unclear. This lack of a complete understanding of the pathogenesis of IgAN has meant that there is still no treatment known to modify mesangial deposition of IgA. Increasing evidence, however, supports the importance of IgA-containing immune complex formation as a pivotal factor driving mesangial IgA deposition and triggering of glomerular injury. A number of potentially important changes to the IgA1 molecule have been identified in IgAN, which may contribute to immune complex formation. These changes suggest that the polymeric IgA1 that deposits in IgA nephropathy is derived from mucosally primed plasma cells. The presence of this IgA in the circulation reflects displacement of mucosal B lineage cells to systemic sites and may be the result of mishoming of lymphocytes trafficking along the mucosa-bone marrow axis.

Coding polymorphisms of bone morphogenetic protein 2 contribute to the development of childhood IgA nephropathy

“…in this study, we did not age-match controls and patients. one of the confounding factors in genetic analysis is the presence of subclinical igan in supposedly normal control populations (2). igan is known to develop in young adults in their twenties.…”

“…The degree of histopathologic injury is extremely variable; this is reflected in the varied pace and severity of clinical presentation noted in this disease. Genetic factors contribute to the development of igan and the progression to renal failure, including the rate of iga deposition, the phenotype of mesangial response and the risk of progressive renal failure (2).…”

IgA Nephropathy: Insights into Genetic Basis and Treatment Options

“…An additional obstacle is the fact that a significant percentage of the patients have only minimal clinical presentation, such as isolated microhematuria, no or minimal proteinuria and normal GFR, and are often not biopsied or even identified. Still no treatment is known to modify mesangial deposition of IgA, which obviously reflects our incomplete knowledge of immunopathogenesis of IgAN [Barratt et al, 2007], and available treatment options are directed mostly at downstream immune and inflammatory events that may lead on to renal scarring. Therefore, as more pathogenetic details, the genetic substrate and heterogeneity of IgAN become increasingly understood, novel treatment strategies with solid therapeutic targets are anticipated, as long as the traditional therapies used until today seem symptomatic rather than etiologic.…”

Update on immunoglobulin A nephropathy, Part I: Pathophysiology

“…The aforementioned mis-homing with transposition of plasma cells from the mucosa to systemic sites might explain this finding [52] . Recently Barratt et al [66,67] postulated the so called hypothesis of the "right antibodies in the wrong place at the wrong time". According this hypothesis, the "right" antigen represented by the mucosal derived GdIgA is in the systemic compartment that is the wrong place.…”