Alterations in circulating measures of Th2 immune responses pre-lung transplant associates with reduced primary graft dysfunction

• Published in: The Journal of heart and lung transplantation
• Main Authors: Schaenman, Joanna M., Weigt, Stephen Samuel, Pan, Mengtong, Lee, Joshua J., Zhou, Xinkai, Elashoff, David, Shino, Michael Y., Reynolds, John M., Budev, Marie, Shah, Pali, Singer, Lianne G., Todd, Jamie L., Snyder, Laurie D., Palmer, Scott, Belperio, John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.07.2024
• Subjects: chemokines; cytokines; lung transplantation; primary graft dysfunction; Th2; cytokines; lung transplantation; chemokines; primary graft dysfunction; Th2; Lung Transplantation; Primary Graft Dysfunction; Cytokines; Chemokines
• ISSN: 1053-2498; 1557-3117; 1557-3117
• DOI: 10.1016/j.healun.2024.07.011

Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pretransplant sera from the multicenter clinical trials in organ transplantation study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (odds ratio [OR] 0.66 [95% confidence interval {CI} 0.45-0.99], p = 0.043), IL-9 (OR 0.68 [95% CI 0.49-0.94], p = 0.019), IL-13 (OR 0.73 [95% CI 0.55-0.96], p = 0.023), and IL-6 (OR 0.74 [95% CI 0.56-0.98], p = 0.036). Multivariable regression performed for each cytokine, including clinically relevant covariables, confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 [95% CI 0.36-0.89], p = 0.014) and IL-10 (OR 0.55 [95% CI 0.32-0.96], p = 0.035). Higher levels of Th2 immune response before lung transplant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pretransplant cytokine assessments could be utilized for recipient risk stratification.