#3862 TGF-β1/ SMAD SIGNALLING IN ANCA ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims The transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine, with distinct roles both in fibrosis and inflammation and acts through the Smad signalling in renal injury. We sought the expression of TGF-β1/Smad signalling in ANCA associated glomerulonephritis (AAGN) and we assessed this expression in correlation with the renal injury at diagnosis as well as the renal progression. Method We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semi-quantitatively and quantitatively using computerized image analysis program in different compartments of 11 renal biopsies with AAGN and the results were statistically analysed with clinicopathological parameters. We also used healthy controls and disease controls with other types of Glomerulonephritis (GN). Results The expression of TGF-β1, pSmad3 and Smad7 were higher in AAGN, compared to healthy controls and other types of GN. The glomerular pSmad3 presented preferable expression at mesangial and endothelial cells and its intensity was correlated with higher chronicity index [global glomerulosclerosis (p<0.001) and interstitial fibrosis (p = 0.03)] (Figure 1). We also reported that the intensity of Smad7 was correlated with higher activity index [cellular crescents (p = 0.03), and fibroid necrosis (p<0.001)] (Figure 2). TGF-β1 expressed at peritubular capillaries around the areas of tubulitis and its expression was correlated with more severe renal injury at diagnosis [higher creatinine (p = 0.019) and proteinuria (p = 0.008)]. At last follow-up (median time 5 years) we reported a significant worst renal function with higher intensity pSmad3 (p = 0.05) and TGF-β1 (p = 0.005), while the expression of Smad7 tended to be beneficial in the maintenance of eGFR (p = 0.055). Conclusion The TGF-β1/Smad signalling is activated in AAGN and its expression is correlated with renal injury both at diagnosis and renal progression.