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

Emily Cerier, Chitaru Kurihara, Taisuke Kaiho, Takahide Toyoda, Adwaiy Manerikar, Viswajit Kandula, Benjamin Thomae, Yuriko Yagi, Anjana Yeldandi, Samuel Kim, Diego Avella-Patino, John Pandolfino, Harris Perlman, Benjamin Singer, G. R. Scott Budinger, Kalvin Lung, Borislav Alexiev, Ankit Bharat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

Original languageEnglish (US)
Pages (from-to)577-590
Number of pages14
JournalAmerican Journal of Transplantation
Volume24
Issue number4
DOIs
StatePublished - Apr 2024

Keywords

  • lung allografts
  • lung transplant
  • primary graft dysfunction

ASJC Scopus subject areas

  • Transplantation
  • Pharmacology (medical)
  • Immunology and Allergy

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