Donor Surfactant Protein A2 Polymorphism and Lung Transplant Survival

PURPOSE: Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the SP-A gene of the donor lung allograft and recipient post-transplant outcome. METHODS: Lung-Tx pts (n=192) were prospectively followed by PFTs, bronchoscopies with BAL and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism by using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. RESULTS: SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as the cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SPA2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at one year (logrank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for one year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on one year survival no significance was observed, indicating that the survival difference were due to the first year's outcome associated with the 1A1 variant. CONCLUSION: Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at one year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.