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Increased eplet mismatch load and reduced immunosuppressive exposure elevate the risk of baseline lung allograft dysfunction

Abstract: Background/Objectives: Some lung transplant (LungTx) recipients do not achieve the expected lung function within the first year, a condition known as baseline lung allograft dysfunction (BLAD). Our objective was to analyze the risk factors associated with BLAD, focusing on the variables associated with a higher risk of developing a more intense alloimmune response. Methods: We carried out a prospective study including 88 LungTx recipients. BLAD was defined as failure to reach 80% of the predicted value for forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC) on two tests conducted at least three weeks apart. Tacrolimus time in therapeutic range (TTR) and mycophenolic acid area under the curve (MPA AUC0-12h) were measured at the third month. Donor-recipient compatibility was assessed using HLA eplet mismatch analysis, performed via HLA Matchmaker 3.1. Results: BLAD patients showed greater eplet mismatch burden (67, IQR 20 vs. 55, IQR 22, p = 0.018) and had been exposed to a lower TTR (26.6%, IQR 14.0% vs. 39.6%, IQR 24.3%, p = 0.039) and less frequently to an adequate third-month MPA AUC0-12 > 30 mg × h/L (57.1% vs. 89.2%, p = 0.020). DR/DQ eplet mismatches (? = -0.348, p = 0.002) and third-month MPA AUC0-12 (? = 0.285, p = 0.009) were independently associated with six-month predicted FEV1%. Conclusions: Among other variables, BLAD and initial lung graft function are associated with greater eplet discordance and lower immunosuppressive drug exposure, suggesting a potential role of underlying alloimmune responses in their pathogenesis.

 Fuente: Journal of Clinical Medicine, 2025, 14(19), 6864

 Publisher: MDPI

 Year of publication: 2025

 No. of pages: 13

 Publication type: Article

 DOI: 10.3390/jcm14196864

 ISSN: 2077-0383

 Publication Url: https://doi.org/10.3390/jcm14196864

Authorship

VÍCTOR MANUEL MORA CUESTA

ELENA GONZALEZ LOPEZ

JAVIER GONZALO OCEJO VIÑALS

DAVID SAN SEGUNDO ARRIBAS

DAVID ITURBE FERNANDEZ

SHEILA IZQUIERDO CUERVO

SANDRA TELLO MENA

MARIA DEL MAR GARCIA SAIZ

MARIA PILAR GARCIA-BERBEL MOLINA

CIFRIÁN, JOSÉ M.