Donor-recipient sex differences: Implications for immunologic outcomes but no impact on survival after lung transplantation

Background Sex-related immunological differences may influence outcomes after lung transplantation, but evidence remains inconsistent. Methods We retrospectively analyzed 252 adults transplanted at the University Hospital Zurich (2015-2024). The primary endpoint was 5-year all-cause mortality; secondary endpoints included acute and chronic rejection, development of donor-specific antibodies (DSA), antibody-mediated rejection (AMR), and post-transplant infectious complications. Results Mean age was 52.2 years. Underlying diagnoses differed by sex (pulmonary fibrosis more common in men, cystic fibrosis in women; p = 0.004). Five-year survival did not differ between sexes (males 56%, females 62%; log-rank p = 0.27) or by donor-recipient sex combination (p = 0.65). Cox regression confirmed that sex and donor-recipient sex interaction were not associated with mortality (recipient sex HR 1.29, 95% CI 0.82-2.03, p = 0.27). Male recipients of female donor lungs had higher rates of de novo DQ-DSA (p = 0.009) and AMR (p = 0.021), whereas female recipients of male lungs more often developed early cellular rejection (p = 0.010). CLAD occurred in 22% without sex-related differences (p=0.316). Infectious complications showed sex-specific bacterial patterns (p = 0.014), with Pseudomonas predominating in males. Conclusion While overall survival was unaffected, sex-specific alloimmune patterns suggest underlying biological differences that warrant further investigation.