Contribution of host-related immune factors to frequency and severity of infections in lung transplant recipients

BACKGROUND: Lung transplantation (LTx) is associated with an increased risk of infection, causing notable morbidity and mortality at all phases post-transplantation. The contribution of host-related immune factors to susceptibility to post-LTx infections is not fully understood. METHODS: The circulating blood profile, serum cytokine profiles and 28 functional single nucleotide polymorphisms in cytokine genes were investigated in 103 lung transplant recipients (LTRs) (men/women: 65/38; mean [95% confidence interval {CI}]: 5.4 [4.7-6.1] years post-LTx) using cytometry and MassARRAY genotyping; the frequency and severity of viral, bacterial and fungal infections were evaluated. RESULTS: In total, 62 (60.2%) LTRs had frequent/severe infections requiring inpatient care (FSI) and 41 (39.8%) had infrequent infections managed in the outpatient setting (IO). We identified rs1800587 AA (IL1A), rs1143634 AA (IL1B), rs16944 GG (IL1B), rs1800795 CG/GG (IL6) and rs1800797 AG/GG (IL6) as being associated with susceptibility to frequent/severe infections in LTRs. A combination of ≥ 2 IL1/IL6 risk variants was present in 53.2% of patients with frequent/severe infections compared with 17.1% with infrequent infections, increasing the likelihood of severe/frequent infections 5.5-fold (95% CI 2.17-13.6; p < 0.001). Moreover, patients with severe/frequent infections exhibited distinct changes in immune cell composition and cytokine profiles between 6- and 12-months post-LTx compared with others. CONCLUSION: Our data demonstrated that LTRs carrying IL1/IL6 risk variants and exhibiting limited post-LTx immune reconstitution were substantially more susceptible to frequent/severe infections. These findings highlight the value of combining immunogenetic profiling with longitudinal immune monitoring to improve infection risk stratification and guide personalised post-LTx care.