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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

 Editorial: MDPI

 Año de publicación: 2025

 Nº de páginas: 13

 Tipo de publicación: Artículo de Revista

 DOI: 10.3390/jcm14196864

 ISSN: 2077-0383

 Url de la publicación: https://doi.org/10.3390/jcm14196864

Autoría

VÍCTOR MANUEL MORA CUESTA

ELENA GONZALEZ LOPEZ

JAVIER GONZALO OCEJO VIÑALS

DAVID ITURBE FERNANDEZ

SHEILA IZQUIERDO CUERVO

SANDRA TELLO MENA

MARIA DEL MAR GARCIA SAIZ

MARIA PILAR GARCIA-BERBEL MOLINA

CIFRIÁN, JOSÉ M.