Aguado Ibáñez Silvia, Sanchez Carlos Almonacid, Ussetti Gil Piedad
Lung Transplant Program, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain.
J Pers Med. 2025 Jun 23;15(7):267. doi: 10.3390/jpm15070267.
Acute cellular rejection (ACR) remains a common complication following lung transplantation and is a major risk factor for chronic lung allograft dysfunction (CLAD). Although transbronchial biopsy (TBB) is the diagnostic gold standard, it is invasive and may be contraindicated in certain patients. This study aimed to assess the diagnostic utility of combining bronchoalveolar lavage fluid (BALF) lymphocyte counts with cytokine profiling-particularly interleukin-17A (IL-17A)-in lung transplant recipients with elevated peripheral blood eosinophil (EOS) counts. : We retrospectively analyzed 108 BALF and matched TBB samples from 74 lung transplant recipients with EOS counts >200 cells/μL, collected between 2014 and 2020. BALF lymphocyte percentages and levels of cytokines (IL-4, IL-6, IL-10, IL-13, IL-15, IL-17A, IFN-γ, TNF) were quantified. Associations with histologically confirmed ACR were evaluated using generalized estimating equation models. : ACR was diagnosed in 57% of TBB samples. BALF lymphocyte percentages were significantly higher in ACR cases (median 8% vs. 4%, < 0.001). Each 1% increase in lymphocytes was associated with a 10% increase in the odds of ACR (OR 1.102; 95% CI 1.076-1.129). IL-17A levels were also significantly elevated in ACR (OR 1.047; 95% CI 1.003-1.092; = 0.032), but with moderate discriminative ability (AUC = 0.629). The combination of BALF lymphocyte counts and IL-17A levels improved diagnostic performance (AUC > 0.76). : The combined assessment of BALF lymphocyte counts and IL-17A levels in recipients with elevated EOS offers a promising non-invasive strategy to support the diagnosis of ACR. Prospective studies are needed to validate these findings and further refine personalized diagnostic approaches to ACR.
急性细胞排斥反应（ACR）仍是肺移植术后常见的并发症，也是慢性肺移植功能障碍（CLAD）的主要危险因素。虽然经支气管活检（TBB）是诊断的金标准，但它具有侵入性，在某些患者中可能是禁忌的。本研究旨在评估将支气管肺泡灌洗液（BALF）淋巴细胞计数与细胞因子谱分析（特别是白细胞介素-17A（IL-17A））相结合，对外周血嗜酸性粒细胞（EOS）计数升高的肺移植受者的诊断效用。我们回顾性分析了2014年至2020年间收集的74例EOS计数>200个细胞/μL的肺移植受者的108份BALF样本及匹配的TBB样本。对BALF淋巴细胞百分比和细胞因子（IL-4、IL-6、IL-10、IL-13、IL-15、IL-17A、IFN-γ、TNF）水平进行了定量分析。使用广义估计方程模型评估与组织学确诊的ACR的相关性。57%的TBB样本诊断为ACR。ACR病例的BALF淋巴细胞百分比显著更高（中位数8%对4%，<0.001）。淋巴细胞每增加1%，ACR的发生几率增加10%（OR 1.102；95%CI 1.076 - 1.129）。ACR中IL-17A水平也显著升高（OR 1.047；95%CI 1.003 - 1.092；P = 0.032），但鉴别能力中等（AUC = 0.629）。BALF淋巴细胞计数和IL-17A水平的联合评估提高了诊断性能（AUC>0.76）。对EOS升高的受者进行BALF淋巴细胞计数和IL-17A水平的联合评估，为支持ACR的诊断提供了一种有前景的非侵入性策略。需要进行前瞻性研究来验证这些发现，并进一步完善ACR的个性化诊断方法。
