#6727 INFLAMMATORY INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY ARE ASSOCIATED WITH HIGHER EXPRESSION OF INTRAGRAFT GRANZYME-B+ AND PHOSPHOSMAD-3+ PROTEIN

Abstract Background and Aims Inflammatory Interstitial fibrosis tubular atrophy (i-IF/TA) is a prominent histological lesion reported in late biopsy poorly associated with graft survival. Cytotoxic T cell secrets Granzyme-B, which cleaves cytoskeleton protein, activates pro-IL-1β, TGF-β into their active form, leading to inflammation, fibrosis, the apoptosis target cell. The association of Granzyme-B+ cytotoxic phospho-SMAD-3 expression has been not explored i-IF/TA depth. Therefore, this study, we aimed determine circulating intragraft profiles together pathway mediator p-SMAD-3 renal transplant recipients (RTRs) patients proven i-IFTA. Method frequency CD3+CD8+Granzyme-B+ (CTLc) was measured by flowcytometry; serum PBMCs culture supernatants Granzyme-B proinflammatory cytokines TGF-β, IL-1β level ELISA, Intragraft mRNA transcript RT-PCR Granzyme-B+, pSMAD-3+ Cell analyzed immunohistochemistry techniques. Independent T-test for continuous variables Pearson correlation applied different variables. Results cytotoxic-T (CD3+CD8+Granzyme-B+) SGF vs (27.96±4.86 23.19±3.85%, p = 0.011), CD3+T (66.08±6.8 65.18±9.35%; 0.68), CD3+CD8+T (37.29±4.11 34.68±5.43%; 0.28). Serum IF/TA (100.82±22.41 130.32±46.60, 0.038 pg/ml), (367.50±31.50 318.81±48.39, 0.005), (49.14±17.03 63.69±23.13, 0.076). (1.01±0.048 2.10±1.02-fold, p<0.001). cell/mm2 count (0.40±0.69 2.20±1.27; 0.001). phosphorylated SMAD-3+ (3.70±1.82 6.73±3.21; 0.008). Fig. 1. positively correlated (r 0.315, 0.047). CTLc negatively urine proteinuria -0.51, p<0.001), creatinine -0.28, P 0.007) eGFR 0.037). While 0.343, 0.001), 0.38, Conclusions Higher T-cell phosphoSMAD-3 positive cells are RTRs.