Abstract
Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also present in patients with IgAV with nephritis, their role in IgAV is disputed. Alternatively, it has been proposed that in IgAV IgA1 antibodies are generated against endothelial cells. We anticipate that such IgA complexes can activate neutrophils via the IgA Fc receptor FcαRI (CD89), thereby inducing neutrophil migration and activation, which ultimately causes tissue damage in IgAV. In this Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other factors such as infections, genetics and the complement system in the pathogenesis of IgA vasculitis.
Highlights
IgA vasculitis (IgAV), referred to as Henoch-Schönlein purpura, is characterized by immunoglobulin A1 (IgA1)-dominant immune deposits affecting small vessels, and often involves skin, gastrointestinal tract, joints, and kidney [1]
Blocking the interaction between IgA and FcαRI was shown to reduce tissue damage in an ex vivo model of linear IgA bullous disease (LABD) [20]. Since both neutrophils and IgA are present in IgA vasculitis lesions, it is likely that the interaction between IgA and FcαRI plays a role in the pathogenesis of IgA vasculitis
It has been hypothesized that IgAV, IgA vasculitis with nephritis (IgAVN) and IgA nephropathy (IgAN) are all entities of the same disease
Summary
IgA vasculitis (IgAV), referred to as Henoch-Schönlein purpura, is characterized by immunoglobulin A1 (IgA1)-dominant immune deposits affecting small vessels, and often involves skin, gastrointestinal tract, joints, and kidney [1]. IgA vasculitis with nephritis (IgAVN) resembles IgA nephropathy (IgAN). Both diseases are characterized by hematuria, proteinuria and immune complex deposition in the glomerular mesangium. Several findings regarding the role of IgA in IgA vasculitis are highlighted, which are summarized in a multi-hit model to explain the pathogeneses of IgAV and IgAVN. This model differs from the multi-hit model which describes the pathomechanisms leading to glomerulonephritis during IgAVN and IgAN. We anticipate that IgA antibodies activate neutrophils via the IgA receptor FcαRI, thereby inducing neutrophil migration and activation, with concomitant tissue damage
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