Pathogenic Role of Anti-HLA Antibodies on Endothelial Progenitor Cell Dysfunction of Highly Sensitized Kidney Transplanted Patients.

V. Cantaluppi,¹ S. Dellepiane,² D. Medica,² G. Tognarelli,² M. Quaglia,¹ C. Musetti,¹ A. Airoldi,¹ L. Biancone.²

¹Nephrology, Dialysis and Kidney Transplantation Unit, University of Eastern Piedmont "A. Avogadro", Novara, Italy
²Nephrology, Dialysis and Kidney Transplantation Unit, University of Torino, Torino, Italy.

Meeting: 2016 American Transplant Congress

Abstract number: A17

Keywords: Antibodies, Endothelial cells, Kidney transplantation, Stem cells

Topic:

Session Information

Session Name: Poster Session A: B cells & AMR, Alloreactivity, Immune Regulation & Regulatory T Cells, T Cell Biology and Alloreactivity, Immunesuppression

Date: Saturday, June 11, 2016

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Halls C&D

Anti-HLA antibodies (abs) bind to kidney graft endothelial cells inducing complement-mediated injury and humoral rejection. Endothelial Progenitor Cells (EPC) are bone marrow-derived precursors able to accelerate tissue regeneration through the release of paracrine mediators such as growth factors and RNA-carrying extracellular vesicles (EV). The aim of this study was to evaluate the potential role of anti-HLA abs on EPC dysfunction in highly sensitized kidney transplanted (KT) patients.

We enrolled in the study 20 KT patients with virtual PRA >80% characterizing anti-HLA abs and relative MFI in comparison to a control KT group (n=10) without abs. Circulating EPC were evaluated by FACS (CD34+/CD133+/flk-1+ cells) and isolated on fibronectin-coated plates studying complement-mediated injury, apoptosis and angiogenesis. In EPC supernatants, VEGF release was evaluated and EV were isolated and characterized for RNA content.

In comparison to control KT, highly sensitized patients presented an increased number of circulating CD34+/CD133+/flk-1+ EPC. However, the isolated EPC showed decreased proliferation and VEGF production. Of interest, also EV concentration, size and RNA content was different from those isolated from EPC of control group: in particular, we observed a significant reduction of pro-angiogenic, anti-apoptotic and complement inhibitor mRNAs (Bcl-XL, eNOS, Akt, CD55, CD59, Factor H) and microRNAs (miR-126, miR-296).

When incubated with plasma collected by highly sensitized KT but not control KT, EPC showed enhanced complement-mediated injury, apoptosis and a reduced angiogenesis activity. These detrimental effects were enhanced by co-incubation with vascular uremic toxins such as ADMA, indoxyl- and p-cresyl-sulphate.

EPC from highly sensitized KT showed several functional alterations induced by anti-HLA abs that may be responsible for a decreased vascular repair during humoral rejection with a consequent premature graft loss due to endothelial rarefaction.

CITATION INFORMATION: Cantaluppi V, Dellepiane S, Medica D, Tognarelli G, Quaglia M, Musetti C, Airoldi A, Biancone L. Pathogenic Role of Anti-HLA Antibodies on Endothelial Progenitor Cell Dysfunction of Highly Sensitized Kidney Transplanted Patients. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Cantaluppi V, Dellepiane S, Medica D, Tognarelli G, Quaglia M, Musetti C, Airoldi A, Biancone L. Pathogenic Role of Anti-HLA Antibodies on Endothelial Progenitor Cell Dysfunction of Highly Sensitized Kidney Transplanted Patients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/pathogenic-role-of-anti-hla-antibodies-on-endothelial-progenitor-cell-dysfunction-of-highly-sensitized-kidney-transplanted-patients/. Accessed June 15, 2021.

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