Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts
Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons - 24(2024), 4 vom: 01. Apr., Seite 577-590 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cerier, Emily [VerfasserIn] |
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| Links: |
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| Themen: |
80295-50-7 |
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| Anmerkungen: |
Date Completed 02.04.2024 Date Revised 02.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ajt.2023.11.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364687673 |
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| 520 | |a Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a lung allografts | |
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| 700 | 1 | |a Kurihara, Chitaru |e verfasserin |4 aut | |
| 700 | 1 | |a Kaiho, Taisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Toyoda, Takahide |e verfasserin |4 aut | |
| 700 | 1 | |a Manerikar, Adwaiy |e verfasserin |4 aut | |
| 700 | 1 | |a Kandula, Viswajit |e verfasserin |4 aut | |
| 700 | 1 | |a Thomae, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Yagi, Yuriko |e verfasserin |4 aut | |
| 700 | 1 | |a Yeldandi, Anjana |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Avella-Patino, Diego |e verfasserin |4 aut | |
| 700 | 1 | |a Pandolfino, John |e verfasserin |4 aut | |
| 700 | 1 | |a Perlman, Harris |e verfasserin |4 aut | |
| 700 | 1 | |a Singer, Benjamin |e verfasserin |4 aut | |
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| 700 | 1 | |a Alexiev, Borislav |e verfasserin |4 aut | |
| 700 | 1 | |a Bharat, Ankit |e verfasserin |4 aut | |
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