Pentraxin-3 Polymorphisms are Associated with Invasive Pulmonary Aspergillosis after Lung Transplantation

Abstract

Purpose Pentraxin-3 (PTX3) polymorphisms influence the risk of invasive pulmonary aspergillosis (IPA) in chronic obstructive pulmonary disease patients, hematopoietic stem cell recipients and solid organs recipients. Therefore, we aimed to investigate this association in a large lung transplant population. Methods Patients who underwent lung transplantation (LTx) between 01/01/2011 and 31/12/2015 in the University Hospitals Leuven were included (n=292). Recipient DNA was successfully extracted from peripheral blood (n=268, 91.8%) or explanted lung tissue (n=24, 8.2%) and successfully genotyped for rs2120243 (n=229, 85.4%), rs2305619 (n=244, 91.0%) and rs3816527 (n=255, 95.1%) polymorphisms using TaqMan® OpenArray® genotyping plates. Cumulative IPA frequency, diagnosed according to ISHLT and EORTC/MSG guidelines, and CLAD-free survival were assessed for each polymorphism. Results Median time of follow-up was 3.3 (1.9-4.5) years; 23% of patients (n=68) developed chronic lung allograft dysfunction (CLAD) after a median time of 2.3 (1.0-3.6) years. Cumulative IPA frequency was significantly higher in rs2120243 AC and AA haplotypes compared to the CC haplotype (15.5% vs 4.5% after 1 year and 28.0% vs 14.9% after 5 years, p=0.024). Cumulative IPA frequency was significantly higher in rs2305619 AG and AA haplotypes compared to the GG haplotype (15.3% vs 4.8% after 1 year and 28.3% vs 12.0% after 5 years, p= 0.032). Cumulative IPA frequency was significantly higher in rs3816527 AC and CC haplotypes compared to the AA haplotype (16.3% vs 3.6% after 1 year and 30.9% vs 10.3% after 5 years, p=0.0028) (figure). There was no difference in CLAD-free survival (p=0.53, p=0.50, p=0.50) between different PTX3 genotypes. Conclusion PTX3 polymorphisms are associated with an increased risk for IPA after LTx.