Pre-existing non-human leukocyte antigen antibodies are associated with allograft rejection after thoracic transplantation

Abstract

BackgroundThere is growing evidence on the important role of non-human leukocyte antigen (HLA) antibodies in lung and heart transplant rejection. Since data on the prevalence and clinical significance of non-HLA antibodies in the Asian population are scarce, we analyzed non-HLA antibodies in heart and lung transplant patients. MethodsWe used the Luminex method to measure non-HLA antibodies in patients who underwent heart transplantation (N = 28) or lung transplantation (N = 36) between 2016 and 2019. We evaluated the association between pre-existing non-HLA antibodies and acute rejection-free days in these recipients. ResultsOf 64 patients, 27 (42.2%) patients underwent rejection, with 26 (40.6%) acute cellular rejection and one (1.6%) acute antibody-mediated rejection. Among 33 identified different non-HLA antibodies, only the anti-glutathione S-transferase theta-1 (GSTT1) antibody positive rate was significantly higher in patients with acute rejection compared to those without rejection (14.8% vs. 0%, p = 0.016). The angiotensin II type I receptor positive rate was not significantly different between the two groups (40% vs. 18.5%, p = 0.129). In the multivariate Cox regression analysis, anti-GSTT1 antibody-positive patients had a higher risk of acute allograft rejection (hazard ratio, 4.19; 95% confidence interval [CI], 1.41–12.49; p = 0.010). The Kaplan-Meier curve showed that anti-GSTT1 antibody-positive patients had fewer acute rejection-free days (χ2 = 7.892; p = 0.005). Additionally, patients who underwent platelet transfusion (odds ratio, 1.49; 95% CI, 1.16–1.91; p = 0.002) before transplantation were more likely to be positive for anti-GSTT1 antibody. ConclusionPatients with antibodies against GSTT1 before heart or lung transplantation have anincreased risk of acute rejection.