2. Academic Validation
  3. A CD31-Derived Peptide Prevents the Development of Antibody-Mediated Lesions in a Rat Model of Aortic Allograft

A CD31-Derived Peptide Prevents the Development of Antibody-Mediated Lesions in a Rat Model of Aortic Allograft

  • Transplant Proc. 2021 Mar;53(2):746-749. doi: 10.1016/j.transproceed.2021.01.003.
Aurélie Sannier 1,  Nathaniel Stroumza 2,  Michael Atlan 3,  Guillaume Even 4,  Kevin Guedj 4,  Jean Sénémaud 5,  Raphaël Coscas 6,  Giuseppina Caligiuri 4,  Antonino Nicoletti 4
Affiliations

Affiliations

  • 1 University of Paris, Institut national de la santé et de la recherche médicale, UMRS1148, Paris, France; Department of Pathology, Assistance publique - hôpitaux de Paris, Bichat Hospital, Paris, France. Electronic address: [email protected].
  • 2 Department of Reconstructive and Aesthetic Plastic Surgery, Assistance publique - hôpitaux de Paris, Tenon Hospital, Paris, France.
  • 3 Department of Reconstructive and Aesthetic Plastic Surgery, Assistance publique - hôpitaux de Paris, Tenon Hospital, Paris, France; Sorbonne University, Paris, France.
  • 4 University of Paris, Institut national de la santé et de la recherche médicale, UMRS1148, Paris, France.
  • 5 University of Paris, Institut national de la santé et de la recherche médicale, UMRS1148, Paris, France; Vascular and Thoracic Surgery Department, Assistance publique - hôpitaux de Paris, Bichat Hospital, Paris, France.
  • 6 Vascular Surgery Department, Assistance publique - hôpitaux de Paris, Ambroise Paré Hospital, Boulogne-Billancourt, France; Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
PMID: 33549347 DOI: 10.1016/j.transproceed.2021.01.003
Abstract

Background: Antibody-mediated rejection (AMR) is a major cause of graft loss. The development of donor-specific Antibodies (DSAs) directed against the allogeneic HLA molecules expressed by the graft also leads to accelerated arteriosclerosis. CD31 is a protein expressed on endothelial and immune cells, ensuring homeostasis at this interface. When strong immune stimulation occurs, the regulatory function of CD31 is lost owing to cleavage of its extracellular portion. P8RI, a synthetic peptide that binds to the ectodomain of CD31, is able to restore the CD31 immunomodulatory function. In this study, we hypothesized that CD31 could represent an attractive molecular target in AMR and investigated whether P8RI could prevent the development of vascular antibody-mediated lesions.

Materials and methods: A rat model of orthotopic aortic allograft was used, and P8RI was administered for 28 days. Circulating DSAs were quantified to assess the alloimmune humoral response, and histologic and immunohistochemical analyses of aortic allografts were performed to estimate antibody-mediated lesions in the allograft.

Results: Aorta-allografted rats receiving P8RI developed fewer DSAs than control Animals (mean fluorescence intensity 344 vs 741). The density of nuclei in the media (3.4 x 10-5 vs 2.2 x 10-5 nuclei/px2) and media surface area (2.33 x 106 vs 2.02 x 106 px2) were higher in Animals treated with P8RI than in control Animals.

Conclusions: These data support a therapeutic potential for molecules able to restore the CD31 signaling to fight AMR. P8RI, an agonist synthetic peptide targeting CD31, might prevent DSA production and have a beneficial effect in limiting arterial antibody-mediated lesions. CD31 agonists may become therapeutic tools to prevent and treat solid organ transplant arteriosclerosis.

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