1029-LBP: Immune responses to Collagen IV and Fibronectin in Renal Transplant Recipients with Transplant Glomerulopathy

Abstract

Antibodies (Abs) to donor HLA (DSA) has been associated with transplant glomerulopathy (TG) following kidney transplantation (KTx). Immune responses to tissue restricted self-antigens (self-Ags) have been proposed to play a role in chronic rejection. In this study we determined the role of kidney restricted self tissue antigens collagen-IV (Col-IV) and fibronectin (FN) in the development of chronic rejection following KTx in TG patients. Biopsy proven 26 KTx TG patients, 10 stable KTx and 14 normal controls were enrolled in this study. Antibodies to self-Ags, Col-IV and FN were determined by ELISA. DSA was determined by solid phase assay and frequency of CD4+ T cells secreting IFN- γ , IL-17 or IL-10 by ELISPOT. Development of Abs to self-Ags following KTx increased the risk for TG with an odds ratio of 22 ( p < 0.01). Abs to self-Ags were IgG and IgM isotypes. Pre-transplant Abs to self-Ags increased the risk of TG (22% vs 10%, p < 0.5). Abs to self-Ags were identified frequently in KTx with DSA. TG patients demonstrated increased Col-IV and FN specific CD4+ T cells secreting IFN- γ (TG: 867 ± 241 pg/mL, stable: 407 ± 178 pg/mL, p = 0.02) and IL-17 (TG: 918 ± 197 pg/mL, stable: 327 ± 142 pg/mL, p = 0.009) with reduction in IL-10 (TG: 184 ± 78 pg/mL, stable: 668 ± 184 pg/mL, p = 0.001). In conclusion, the development of Abs to self-Ags is an independent risk factor and having both DSA and Abs to self-Ags increases the risk for TG. The increased frequency of self-Ag specific IFN- γ and IL-17 cells with reduction in IL-10 demonstrate tolerance breakdown to self-Ags which we propose play a role in the pathogenesis of TG.