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.