Association between CLAD phenotype and KIR genotypes in lung transplant recipients

Results from a retrospective, single-center study evaluating the association between specific human leukocyte antigen (HLA)–killer immunoglobulin-like receptor (KIR) interactions and distinct chronic lung allograft dysfunction (CLAD) phenotypes in bilateral lung transplant recipients were presented by Samuel Robinson at the 31st International Congress of The Transplantation Society (TTS), September 20–23, 2026, Sydney, AU. 

Key data: Among 127 patients with CLAD, 83 had bronchiolitis obliterans syndrome (BOS) and 44 had restrictive allograft syndrome (RAS). Median Predicted Indirectly Recognizable HLA Epitopes II (PIRCHE-II) scores were significantly higher in patients with BOS vs RAS (p < 0.05), whereas verified eplet mismatch (epMM) scores did not significantly differ between the groups. Expression of KIR2DS2 and KIR2DL2 was higher in patients with RAS vs BOS (both p < 0.05). Among patients with RAS, KIR2DL2 positivity was associated with improved survival (adjusted hazard ratio [aHR], 0.30; 95% confidence interval [CI], 0.11–0.83; p = 0.020), as was Bw4 mismatch (aHR, 0.31; 95% CI, 0.09–0.98; p = 0.047), while cytomegalovirus (CMV) seropositivity was associated with poorer survival (aHR, 2.70; 95% CI 1.04–7.01; p = 0.041).

Key learning: Results from this study suggest that differences in KIR expression and PIRCHE-II scores in patients with BOS and RAS may reflect unique pathological mechanisms underlying these CLAD subtypes. Larger, multicenter studies are needed to confirm these findings.