HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice

S. Galvani, N. Augé, D. Calise, J. C. Thiers, C. Canivet, N. Kamar, L. Rostaing, M. Abbal, F. Sallusto, R. Salvayre, T. Böhler, Y. Zou, P. Stastny, A. Nègre-Salvayre, M. Thomsen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.

Original languageEnglish (US)
Pages (from-to)2607-2614
Number of pages8
JournalAmerican Journal of Transplantation
Volume9
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Arteriosclerosis
Immunoglobulin Isotypes
Blood Vessels
Arteries
Transplants
Antibodies
Smooth Muscle Myocytes
Monoclonal Antibodies
Mesenteric Arteries
SCID Mice
Cellular Immunity
Allografts
Cell Proliferation
Tissue Donors
Injections

Keywords

  • Allograft arteriosclerosis
  • Animal models
  • Anti-HLA antibodies
  • Antibody-mediated rejection
  • Chronic allograft rejection
  • Smooth muscle cells

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice. / Galvani, S.; Augé, N.; Calise, D.; Thiers, J. C.; Canivet, C.; Kamar, N.; Rostaing, L.; Abbal, M.; Sallusto, F.; Salvayre, R.; Böhler, T.; Zou, Y.; Stastny, P.; Nègre-Salvayre, A.; Thomsen, M.

In: American Journal of Transplantation, Vol. 9, No. 11, 11.2009, p. 2607-2614.

Research output: Contribution to journalArticle

Galvani, S, Augé, N, Calise, D, Thiers, JC, Canivet, C, Kamar, N, Rostaing, L, Abbal, M, Sallusto, F, Salvayre, R, Böhler, T, Zou, Y, Stastny, P, Nègre-Salvayre, A & Thomsen, M 2009, 'HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice', American Journal of Transplantation, vol. 9, no. 11, pp. 2607-2614. https://doi.org/10.1111/j.1600-6143.2009.02804.x
Galvani, S. ; Augé, N. ; Calise, D. ; Thiers, J. C. ; Canivet, C. ; Kamar, N. ; Rostaing, L. ; Abbal, M. ; Sallusto, F. ; Salvayre, R. ; Böhler, T. ; Zou, Y. ; Stastny, P. ; Nègre-Salvayre, A. ; Thomsen, M. / HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice. In: American Journal of Transplantation. 2009 ; Vol. 9, No. 11. pp. 2607-2614.
@article{49aa211d2e024c65b054bc2aba8026e2,
title = "HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice",
abstract = "Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.",
keywords = "Allograft arteriosclerosis, Animal models, Anti-HLA antibodies, Antibody-mediated rejection, Chronic allograft rejection, Smooth muscle cells",
author = "S. Galvani and N. Aug{\'e} and D. Calise and Thiers, {J. C.} and C. Canivet and N. Kamar and L. Rostaing and M. Abbal and F. Sallusto and R. Salvayre and T. B{\"o}hler and Y. Zou and P. Stastny and A. N{\`e}gre-Salvayre and M. Thomsen",
year = "2009",
month = "11",
doi = "10.1111/j.1600-6143.2009.02804.x",
language = "English (US)",
volume = "9",
pages = "2607--2614",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - HLA class i antibodies provoke graft arteriosclerosis in human arteries transplanted into scid/beige mice

AU - Galvani, S.

AU - Augé, N.

AU - Calise, D.

AU - Thiers, J. C.

AU - Canivet, C.

AU - Kamar, N.

AU - Rostaing, L.

AU - Abbal, M.

AU - Sallusto, F.

AU - Salvayre, R.

AU - Böhler, T.

AU - Zou, Y.

AU - Stastny, P.

AU - Nègre-Salvayre, A.

AU - Thomsen, M.

PY - 2009/11

Y1 - 2009/11

N2 - Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.

AB - Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.

KW - Allograft arteriosclerosis

KW - Animal models

KW - Anti-HLA antibodies

KW - Antibody-mediated rejection

KW - Chronic allograft rejection

KW - Smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=70350129078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70350129078&partnerID=8YFLogxK

U2 - 10.1111/j.1600-6143.2009.02804.x

DO - 10.1111/j.1600-6143.2009.02804.x

M3 - Article

C2 - 19843036

AN - SCOPUS:70350129078

VL - 9

SP - 2607

EP - 2614

JO - American Journal of Transplantation

JF - American Journal of Transplantation

SN - 1600-6135

IS - 11

ER -