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Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung

Emily Cerier1, Chitaru Kurihara1, Taisuke Kaiho1

  • 1Department of Thoracic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|November 17, 2023
PubMed
Summary

Early complement activation after lung transplant, indicated by C4d staining, strongly predicts severe primary graft dysfunction (PGD). This finding supports exploring complement inhibition to improve transplant outcomes.

Keywords:
lung allograftslung transplantprimary graft dysfunction

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Area of Science:

  • Transplantation immunology
  • Pathogenesis of organ injury
  • Complement system research

Background:

  • Primary graft dysfunction (PGD) is a major complication after lung transplantation.
  • The complement system is increasingly implicated in PGD pathogenesis.
  • Early complement activation may be a key driver of severe PGD and poor outcomes.

Purpose of the Study:

  • To investigate the association between early complement activation postreperfusion and the development of severe PGD grade 3 (PGD-3) at 72 hours.
  • To determine if early C4d deposition predicts PGD-3 and long-term transplant outcomes.

Main Methods:

  • Prospective study of 253 lung transplant recipients from January 2018 to June 2023.
  • Allograft biopsies were performed at the end of cold ischemia and 30 minutes postreperfusion.
  • C4d staining assessed for complement deposition; PGD-3 evaluated at 72 hours.

Main Results:

  • PGD-3 occurred in 14% of patients.
  • Positive C4d staining postreperfusion was significantly more common in patients who developed PGD-3 (51% vs 12%, P < .001).
  • Positive C4d staining predicted PGD-3 (OR 7.92, P < .001) and worse long-term outcomes.

Conclusions:

  • Early complement deposition in lung allografts is a strong predictor of PGD-3 at 72 hours.
  • These findings highlight the critical role of the early complement response in PGD development.
  • Further research into complement inhibition strategies is warranted to mitigate PGD and enhance transplant success.