Risk Factors for the Development of Early Anti-HLA Donor Specific Antibodies After Lung Transplantation: The Role of Primary Graft Dysfunction

Abstract

<h3>Purpose</h3> The development of anti-HLA donor specific antibodies (DSA) after lung transplantation has been associated poor graft survival. DSA may develop early after lung transplantation or later, usually when chronic lung allograft dysfunction (CLAD) ensues. Early DSA have recently been considered a product of a memory rather than a de-novo reaction after alloantigen exposure. Aim of this study was to analyse the risk factors for the development of early DSA after lung transplantation. <h3>Methods</h3> Records of patients transplanted at our institution between 01/2013 and 10/2021 were retrospectively reviewed. Patients were controlled for eDSA every two weeks after transplantation until hospital discharge, using the Luminex single-antigen test (mean fluorescence index threshold, 1000). Multivariable binary logistic regression analysis, including variables with univariable p-value <0.10, was performed to identify factors associated with eDSA. Goodness-of-fit of the model was tested using the Hoshmer and Lemeshow (H-L) test. <h3>Results</h3> During the study period, among the 1007 lung-transplanted patients, 275 (27%) patients showed early detectable DSA (preformed, n=56; de-novo, n=254; class I, n=71; class II, n=239). Median (IQR) time to DSA detection was 14 (11-21) days. The binary logistic regression analysis showed that pediatric (<18 years old) transplantation (OR: 2.2, 95%CI: 1.8-2.8, p=0.001), presence of pretransplant HLA antibodies (OR: 2.1, 95%CI: 1.6-2.8, p<0.01), donor lung preservation with Organ Care System (OR: 0.37, 95%CI: 0.14-0.97, p=0.04), and primary graft dysfunction (PGD) score grade 2-3 at 72 hours after transplantation (OR: 1.8, 95%CI: 1.2-1.8, p=0.007) were associated with eDSA detection (H-L statistic, p=0.92). <h3>Conclusion</h3> The graft damage and donor antigen exposure provoked by primary graft dysfunction may lead to eDSA production, that should not be considered only a product of a memory but also of a de-novo reaction (Figure 1).