The activation of PARP is well considered to play an augmenting role in inflammation. However, its role in the development of fibrosis is not well defined. The aim of this study was to investigate the role and mechanism of PARP both in inflammation and interstitial fibrosis (IF) processes in recipients with antibody-mediated rejection (AMR).

Among 100 patients 54 had pure AMR (Group 1) while 46 had both AMR and acute vascular rejection (Group 2). PARP, α-SMA, TNF-α, TGF-β and HLA-DR expression of tubules were studied. Also, infiltrated inflammatory cells in the peritubular capillaries (PTCs) and interstitium highlighted with PARP, TNF-α, HLA-DR, and CD68. Follow-up biopsies analyzed for the development of diffuse IF.

Group 2 showed higher degrees of tubular PARP, α-SMA, TNF-α, TGF-β, and HLA-DR expression compared to Group 1 (p<0.01). PARP, TNF-α and HLA-DR positive infiltrated cells and macrophage infiltration both in interstitium and PTCs were found to be higher in Group 2 compared to Group 1 (p<0.001).The extensity of PTC C4d expression increased with increasing degree of leukocyte and macrophage infiltration both in PTCs and interstitium (p<0.001). The time of the development of IF decreased with increasing intensity of PTC and interstitial leukocyte and macrophage infiltration (p<0.001). Also, the development of IF shortened with increasing PARP, HLA-DR, TNF-α expression in inflammatory cells and increasing PARP, α-SMA, TNF-α, TGF-β, HLA-DR expression in tubular cells (P<0.01). Tubular and interstitial PARP expressions showed significant association with tubular α-SMA, TNF-α, TGF-β, and HLA-DR expressions (P<0.01). PARP expression on both tubules and inflammatory cells showed poor graft outcome (p<0.01). The 5-year graft survival was 96% for recipients with negative tubular PARP while it was 60%, 19% and 18% for recipients with grade 1, 2 and 3 tubular PARP expression respectively (p<0.001).

In conclusion increased PARP activation leads to early graft loss with augmenting inflammation and interstitial fibrosis via activation of inflammatory signaling pathways and myofibroblastic differentiation of tubular cells. Therefore we suggest that PARP inhibitor drugs can combine with immunosuppressive therapy to control both inflammation and fibrosis to prevent early graft loss.

CITATION INFORMATION: Ozdemir B, Ozdemir F, Baskin E, Haberal M. Predictive Value of Renal Poly (ADP-Ribose) Polymerase (PARP) Expression Both in Inflammation and Interstitial Fibrosis Processes in Recipients with Antibody-Mediated Rejection. Am J Transplant. 2017;17 (suppl 3).

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