AUTHOR=Novysedlak Rene , Balko Jan , Tavandzis Janis , Tovazhnianska Vira , Slavcev Antonij , Vychytilova Katerina , Smetanova Jitka , Bohyn Alexandre , Vajter Jaromir , Borcinova Martina , Vanaudenaerde Bart M. , Lischke Robert , Vachtenheim Jiri , Ceulemans Laurens J. , Ozaniak Strizova Zuzana TITLE=Elevated PD-L1 and PECAM-1 as Diagnostic Biomarkers of Acute Rejection in Lung Transplantation JOURNAL=Transplant International VOLUME=37 YEAR=2024 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2024.13796 DOI=10.3389/ti.2024.13796 ISSN=1432-2277 ABSTRACT=

Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.