An update on the pathogenesis and treatment of IgA nephropathy.

Over the past two decades significant progress has been made in unravelling the complex pathogenesis of immunoglobulin A nephropathy (IgAN). Excess amounts of poorly galactosylated immunoglobulin (Ig)A1 in the serum appear to be the trigger for generation of glycan-specific IgG and IgA autoantibodies, resulting in the formation of circulating IgA immune complexes, which are pivotal to the development of nephritis. It remains unclear why there is an increase in poorly galactosylated IgA1 molecules in the serum in IgAN.

Inherited IgA glycosylation pattern in IgA nephropathy and HSP nephritis: where do we go next?

New data from Kiryluk et al. show the importance of genetic factors in determining the profile of serum IgA1 O-glycoforms in IgA nephropathy and Henoch-Schönlein purpura nephritis. Elevated serum levels of poorly galactosylated IgA1 O-glycoforms do not, however, appear sufficient in themselves to cause nephritis in these two diseases, and a 'second hit' is necessary before changes in IgA1 glycosylation translate into clinical disease.

Immune complex formation in IgA nephropathy: CD89 a 'saint' or a 'sinner'?

New data suggest that a soluble form of the IgA receptor CD89 may be protective against development of progressive renal injury in IgA nephropathy (IgAN). Understanding how IgA triggers shedding of CD89 from myeloid cell surfaces could help clarify the process of immune complex formation in IgAN, and measurement of this soluble form of CD89 may in the future prove a useful prognostic indicator of end-stage renal disease in this common glomerulonephritis.