Plasma Levels of Histidine-Rich Glycoprotein are Associated with the Development of Primary Graft Dysfunction after Lung Transplantation

Abstract

<h3>Purpose</h3> Histidine-rich glycoprotein (HRG) is a 75 kDa plasma glycoprotein produced in and secreted from the liver. Recently, supplementary HRG treatment has been shown to inhibit acute respiratory distress syndrome (ARDS) and prevent septic lethality. The pathogenesis of primary graft dysfunction (PGD) after lung transplantation (LT) could be similar to that of ARDS. However, the relationship between plasma levels of HRG and PGD after LT remains unknown. <h3>Methods</h3> Blood samples were collected from a total of 68 patients who underwent LT, including the patients with PGD grade 0-1 (the non-PGD group, n = 43), those with PGD grade 2 (the moderate PGD group, n = 18) and those with PGD grade 3 (the severe PGD group, n = 7) at 72 hours after LT. Plasma levels of HRG were quantified using ELISA and compared among the three groups. Appropriate cut-off values of HRG levels were set for overall survival (OS) after LT. <h3>Results</h3> The median follow-up period was 1208 (286-2982) days. Plasma levels of HRG at 72 hours after LT in the severe PGD group were significantly lower than those of the other groups (the non-PGD group vs. the severe PGD group, P = 0.042; the moderate PGD group vs. the severe PGD group, P = 0.040) (Fig. 1). An ROC analysis of the performance of plasma levels of HRG as a marker of overall survival yielded an AUC of 0.61 at a threshold level of 34.4 µg/mL. Patients with plasma levels of HRG ≥ 34.4 µg/mL showed significantly better OS and chronic lung allograft dysfunction (CLAD) free survival than those with plasma levels of HRG < 34.4 µg/mL (OS, P = 0.037; CLAD-free survival, P = 0.046) (Fig. 2). <h3>Conclusion</h3> Plasma level of HRG at 72 hours after LT was associated with the development of PGD, suggesting its usefulness as a predictor of the development of CLAD and survival after LT.