The results of the present study indicate that the genetic variations and gene expression level of TNFSF13 are associated with the susceptibility and severity of IgAN in a Han Chinese population.
Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF.
TGF-beta 1 mRNA was detected in 68% (24 of 35) of patients with active, and 70% (7 of 10) inactive IgA nephropathy, but in only 18% (3 of 17) normal (P < 0.005), and 27% (4 of 15) disease controls.
These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-beta production and development of glomerular injury in IgAN.
Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001).
Although a close relationship between increased renal tissue levels of TGF-beta1 and fibronectin has been reported in IgA nephropathy, no data are available on renal tissue expression of Rho proteins.
The expression of transforming growth factor beta 1, stromelysin and tissue inhibitor of matrix proteinase 1 in the glomeruli was decreased in diabetic patients with advanced tissue damage, but they were progressively expressed in the advanced stage of IgA nephropathy.
Reduced ACE2 expression (p < 0.01) and increased ACE expression in glomeruli (p < 0.001), and reduced ACE2 expression in tubulointerstitium (p < 0.001) were observed in patients with IgA nephropathy compared to healthy controls, although the changes in ACE2 mRNA were not statistically significant.
Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA.
Expression of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P = 0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n = 12) (r = 0.37, P = 0.007).
The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.
Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001).
IgG-ddIgA1 complexes from both patients with IgA nephropathy (IgAN-IgG-dd-IgA1) and healthy controls (HC-IgG-dd-IgA1) could induce the proliferation of mesangial cells and up-regulate expression of MCP-1, IL-6 and CXCL1.
However, plasma BAFF levels were positively associated with serum creatinine, proteinuria, uric acid and group A Streptococcus infection index in patients with IgAN.