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

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.

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.

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.

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.