Although the molecular features of human IgA1 are different from rodent IgA, human IgA1 knock-in (α1KI)-CD89 transgenic mice, which express both human IgA1 and CD89, show circulating and mesangial deposits of IgA1-soluble CD89 complexes that result in kidney inflammation, hematuria, and proteinuria.
The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients.
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.