Glomerular deposits of Von Willebrand factor (vWF) and loss of endothelial cell surface antigens on peritubular capillaries (PTCs) showed a strong association with worse graft outcome in recipients with antibody-mediated rejection (ABMR)
B. Handan Ozdemir1, F. Nurhan Ozdemir2, Alev Ok Atilgan1, Eda Akcay1, Esra Baskin3, Mehmet A. Haberal4.
1Pathology, Baskent University, Ankara, Turkey; 2Nephrology, Baskent University, Ankara, Turkey; 3Pediatric Nephrology, Baskent University, Ankara, Turkey; 4Transplantation, Baskent University, Ankara, Turkey
Introduction: Endothelial cells (ECs) are the only cell of donor origin that come in contact with circulating antibodies. Expression of CD31, vWF, VEGF, and HLA-DR on ECs are well-documented. ECs of PTCs usually stained for CD31, vWF, and HLA-DR. Although ECs of glomeruli were always strongly positive for CD31 and HLA-DR, they were rarely positive for vWF. Neither EC surface antigen was reported to be express in the mesangium. We aimed to evaluate the diagnostic and prognostic importance of EC surface antigens in renal allografts with ABMR.
Methods: Biopsies of 104 recipients with ABMR scored for microvascular inflammation (MV) and C4d expression. Glomerular and PTC leukocyte and macrophage infiltration graded. HLA-DR, CD31, vWF, and VEGF expression studied to show the presence or absence of EC surface antigens on glomeruli and PTCs. Loss of EC antigens on PTC accepted as PTC destruction.
Follow-up biopsies analyzed for the development of transplant glomerulopathy (TG), glomerulosclerosis (GS) (> 30% of glomeruli), and interstitial fibrosis (IF).
Results: The degree of C4d expression showed a significant correlation with the degree glomerular and PTC leukocyte and macrophage infiltration (p<0.001). Both the glomerular and PTC expression of CD31, HLA-DR and VEGF found to decrease with an increasing degree of MV macrophage and leukocyte infiltration (p<0.001). With an increasing degree of MV inflammation, the glomerular expression of vWF increases, while the PTC expression of vWF decreases (p<0.001). Decreasing degree of PTC expression of HLA-DR, CD31, vWF, and VEGF expression and increasing grade of glomerular vWF found to show increasing incidence of TG, GS, and IF (p<0.001). The mean time of graft survival found to decrease with increasing grade of glomerular vWF and decreasing grade of PTC HLA-DR, CD31, vWF, and VEGF expression (P<0.001).
Conclusion: Glomerular deposits of vWF and loss of EC surface antigens on PTCs showed a strong association with the development of TG, GS, IF and worse graft outcomes in recipients with ABMR. Thus glomerular deposits of VWF and PTC destruction together may be a marker for the development of early TG, GS, and IF and may help to determine patients who need further treatment.
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