부산대학교 도서관

Aim: 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. Methods: 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- , IL-17 or IL-10 by ELISPOT. Results: 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- (TG: 867±241pg/mL, stable: 407±178pg/mL, p =0.02) and IL-17 (TG: 918±197pg/mL, stable: 327±142pg/mL, p=0.009) with reduction in IL-10 (TG: 184 78 pg/mL, stable: 668 184 pg/mL, p =0.001). Conclusions: 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- 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. [ABSTRACT FROM AUTHOR]