The pathogenesis of
IgA nephropathy (IgAN) may be associated with the mesangial deposition of aberrantly glycosylated
IgA1. To identify mediators affected by aberrantly glycosylated
IgA1 in cultured human mesangial cells (HMCs), we generated enzymatically modified desialylated and degalactosylated (deSial/deGal)
IgA1. The state of deglycosylated
IgA1 was confirmed by
lectin binding to Helix aspersa (HAA) and Sambucus nigra (SNA). In the
cytokine array analysis, 52
proteins were upregulated and 34 were downregulated in HMCs after stimulation with deSial/deGal
IgA1. Among them, the secretion of
adiponectin was suppressed in HMCs after stimulation with deSial/deGal
IgA1. HMCs expressed mRNAs for
adiponectin and its type 1 receptor, but not the type 2 receptor. Moreover, we revealed a downregulation of
adiponectin expression in the glomeruli of renal biopsy specimens from patients with IgAN compared to those with
lupus nephritis. We also demonstrated that aberrantly glycosylated
IgA1 was deposited in the mesangium of patients with IgAN by dual staining of HAA and
IgA. Moreover, the urinary HAA/SNA ratio of
lectin binding was significantly higher in IgAN compared to other
kidney diseases. Since
adiponectin has anti-inflammatory effects, including the inhibition of adhesion molecules and
cytokines, these data suggest that the local suppression of this
adipokine by aberrantly glycosylated
IgA1 could be involved in the regulation of glomerular
inflammation and
sclerosis in IgAN.