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-纬, 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-纬 (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-纬 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.