Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Jan 10:13:1024021.
doi: 10.3389/fimmu.2022.1024021. eCollection 2022.

PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection

Ilaria Righi  1 , Valentina Vaira  2   3 , Letizia Corinna Morlacchi  4 , Giorgio Alberto Croci  2   3 , Valeria Rossetti  4 , Francesco Blasi  3   4 , Stefano Ferrero  2   5 , Mario Nosotti  1   3 , Lorenzo Rosso  1   3 , Mario Clerici  3   6
Affiliations
Observational Study

PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection

Ilaria Righi et al. Front Immunol. .

Abstract

Introduction: Chronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has been scarcely investigated in the setting of lung transplantation.

Methods: We conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules.

Results: Results showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome.

Discussion: Results of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.

Keywords: PD-1; chronic rejection; immune checkpoint molecules; immunology; lung transplantation.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PD1 is a marker of poor allograft outcome in transbronchial cryobiopsies of LTx patients. (A) Representative images of TCB with a lymphocytic infiltrate positive for PD1 (>5% of positive lymphocytes; upper panel) or negative (≤5% of positive lymphocytes; lower panel). Scale bars, 100 μm. (B) Correlation of PD1-positive TCB with histological diagnosis of acute rejection (hAR grade A). P value is from Fisher exact test. (C) Presence of eosinophilia in BAL was correlated with PD1-positive TCB. Each dot is a case and lines indicate median with IQR. P value is from Mann-Whitney U test. (D) Correlation of PD1-positive TCB with occurrence of chronic lung allograft dysfunction (CLAD) during follow-up. P value is from Fisher exact test.
Figure 2
Figure 2
Schematic of TCB patients’ series. hAR, Histological diagnosis of acute rejection (grade A); CLAD, chronic lung allograft dysfunction; PD1, Programmed cell death protein 1; BOS, bronchiolitis obliterans syndrome; RAS, restrictive allograft syndrome.
See this image and copyright information in PMC

References

    1. Tissot A, Danger R, Claustre J, Magnan A, Brouard S. Early identification of chronic lung allograft dysfunction: The need of biomarkers. Front Immunol (2019) 10:1681. doi: 10.3389/fimmu.2019.01681 - DOI - PMC - PubMed
    1. Koutsokera A, Royer PJ, Antonietti JP, Fritz A, Benden C, Aubert JD, et al. . Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation. Front Med (2017) 4:109. doi: 10.3389/fmed.2017.00109 - DOI - PMC - PubMed
    1. Hachem RR, Khalifah AP, Chakinala MM, Yusen RD, Aloush AA, Mohanakumar T, et al. . The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation (2005) 80(10):1406–13. doi: 10.1097/01.tp.0000181161.60638.fa - DOI - PubMed
    1. Verleden SE, Ruttens D, Vandermeulen E, Bellon H, Van Raemdonck DE, Dupont LJ, et al. . Restrictive chronic lung allograft dysfunction: where are we now? J Heart Lung Transplant (2015) 34:625–30. doi: 10.1016/j.healun.2014.11.007 - DOI - PubMed
    1. Glanville AR, Verleden GM, Todd JL, Benden C, Calabrese F, Gottlieb J, et al. . Chronic lung allograft dysfunction: Definition and update of restrictive allograft syndrome-a consensus report from the pulmonary council of the ISHLT. J Heart Lung Transplant (2019) 38(5):483–92. doi: 10.1016/j.healun.2019.03.008 - DOI - PubMed

Publication types

Substances