Antibody and complement mediated injury in transplants following sensitization by allogeneic blood transfusion

Zhiping Qian, Chih Yuan Lee, Kazunori Murata, Jinhuan Liu, Karen Fox-Talbot, Barbara A. Wasowska, William M. Baldwin

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Many patients on the waiting list for transplants are sensitized from previous blood transfusions, pregnancy, or transplants. We investigated the role of complement in acute and chronic pathology in hearts transplanted to sensitized rats. METHODS. Blood was transfused from allogeneic PVG.R8 rats or control isogeneic PVG.1U rats to C6-sufficient and -deficient PVG.1U rats. Three weeks later hearts were transplanted from PVG.R8 donors and low-dose cyclosporin A was initiated. RESULTS. Allogeneic but not isogeneic blood transfusion elicited strong immunoglobulin (Ig) M, IgG1 and IgG2b alloantibody responses. Sensitization caused accelerated acute rejection of cardiac allografts by C6-sufficient recipients (4 days). In contrast, allografts functioned over 40 days in all C6-deficient recipients, but sensitization caused increased interstitial fibrosis and chronic vasculopathy. Circulating alloantibodies were associated with deposits of C4d on the vascular endothelium together with pericapillary accumulation of neutrophils and macrophages in the grafts. In contrast, T cells accumulated in periarterial lymphatics that did not have C4d deposits. CONCLUSIONS. Presensitization by allogeneic blood transfusion causes accelerated acute graft rejection in the presence of the complete complement cascade. In the absence of C6, macrophages colocalized with deposits of C4d and T cells accumulated in the periarterial lymphatics.

Original languageEnglish (US)
Pages (from-to)857-864
Number of pages8
JournalTransplantation
Volume82
Issue number7
DOIs
Publication statusPublished - Oct 2006

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Keywords

  • C4d
  • C6
  • Complement
  • Donor specific alloantibodies
  • Macrophages

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Qian, Z., Lee, C. Y., Murata, K., Liu, J., Fox-Talbot, K., Wasowska, B. A., & Baldwin, W. M. (2006). Antibody and complement mediated injury in transplants following sensitization by allogeneic blood transfusion. Transplantation, 82(7), 857-864. https://doi.org/10.1097/01.tp.0000232335.06792.35