Frank D'Ovidio, Joanna Floros, Beatrice Aramini, David Lederer, Susan L. DiAngelo, Selim Arcasoy, Joshua R. Sonett, Hillary Robbins, Lory Shah, Joseph Costa, Andreacarola Urso
European Respiratory Journal 2020 55: 1900618; DOI: 10.1183/13993003.00618-2019
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 surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome.
Methods Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism 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 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 SP-A2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was 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 1 year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.
Donor genetic polymorphisms of the lung-specific innate defence systems determine post-lung transplant recipient outcome http://bit.ly/2QNpX7Q
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: F. D'Ovidio reports grants from NIH-NHLBI, during the conduct of the study.
Conflict of interest: J. Floros has nothing to disclose.
Conflict of interest: B. Aramini has nothing to disclose.
Conflict of interest: D. Lederer has nothing to disclose.
Conflict of interest: S.L. DiAngelo has nothing to disclose.
Conflict of interest: S. Arcasoy has nothing to disclose.
Conflict of interest: J.R. Sonett has nothing to disclose.
Conflict of interest: H. Robbins has nothing to disclose.
Conflict of interest: L. Shah has nothing to disclose.
Conflict of interest: J. Costa has nothing to disclose.
Conflict of interest: A. Urso has nothing to disclose.
Support statement: This work was supported by the National Institutes of Health, NHLBI, R21HL092478-01A2; HL34788. Funding information for this article has been deposited with the Crossref Funder Registry.