ACE deletion polymorphism is associated with a high risk of non-infectious pulmonary complications after stem cell transplantation

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Non-infectious pulmonary complication (NIPC) is a serious adverse event for allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. NIPC includes both categories of lung complications: early onset idiopathic pneumonia syndrome (IPS) (onset <120days) and late-onset non-infectious pulmonary complications (LONIPCs). Both categories have high mortality and morbidity rates, and critical treatments are not available. The renin-angiotensin system plays a critical role in pulmonary fibrosis. We, therefore, studied the relationship between angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphisms and NIPC incidence in 149 consecutive allo-HSCT recipients. A total of 12.1% (18/149) of these patients were diagnosed with NIPC (IPS, 3; LONIPCs, 15). Eight NIPC patients died from respiratory failure (mortality rate, 44.4%). Peripheral blood stem cell transplantation was associated with a significantly higher incidence of NIPC than bone marrow transplantation and cord blood transplantation by univariate analysis (HR 3.13, P=0.031). The serum ACE levels differed significantly according to the ACE insertion/deletion polymorphism. Patients with an ACE D/D genotype occurred at a significantly higher frequency among NIPC patients than I/D and I/I patients (HR 9.03, P<0.0001). Multivariate analysis confirmed that NIPC is associated with ACE D/D genotypes (HR 8.8, P<0.001). Our data support a role for the renin-angiotensin system in the pathogenesis of NIPC after allo-HSCT, and may represent a therapeutic target for complications.