With this as background, we investigated how TLR9 activation in IgA secreting cells results in overproduction of nephritogenic IgA in the IgAN-prone ddY mouse and in human IgA1-secreting cells.
Next, we evaluated the IgA1 O-glycan structure of serum IgA from IgAN recipients (n = 26), IgAD donors (n = 17), and non-IgAD helthy donors (n = 27) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).
Immunoglobulin A nephropathy (IgAN) is considered as mesangiopathy since it initiates in the mesangium; however, other glomerular components are involved and the glomerular capillary wall offers the first contact to circulating macromolecular IgA1.
Median serum Gd-IgA1 levels were significantly higher in IgAN patients [13135.6(2723.3,59603.8)ng/ml] compared to those with non IgA glomerular disease [4954.8(892.9,18256.2) ng/ml] and healthy controls [6299.5(1993.2,19256) ng/ml] and this was observed even after log transformation and adjustment for age and gender(p<0.0001).
Many studies have demonstrated that galactose-deficient IgA1 (Gd-IgA1) in the IgA1 hinge region is associated with the development and also progression of primary IgAN.
These data support an essential role of the gut microbiota in the generation of mucosa-derived nephrotoxic IgA1 and in IgAN development, opening new avenues for therapeutic approaches in this disease.
We identified and demonstrated that GM130 plays an important role in IgA1 O-glycans deficiency in IgAN patients, by negatively regulating C1GALT1 expression.
Both ABO blood group antigens and pathogenic immunoglobulin A1 (IgA1) in patients with IgA nephropathy (IgAN) are influenced by modifications of N-acetylgalactosamine and galactose.
The prednisone therapy reduces overall aberrancy in IgA1 O-glycosylation in IgA nephropathy patients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients.
In this article, we review studies concerning IgA1 O-glycosylation that have contributed to the current understanding of the role of IgA1 in the pathogenesis of IgA nephropathy.