BALF Lymphocyte and Cytokine Profiling as Biomarkers of Acute Rejection After Lung Transplantation

Background: 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. Methods: 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. Results: ACR was diagnosed in 57% of TBB samples. BALF lymphocyte percentages were significantly higher in ACR cases (median 8% vs. 4%, p < 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; p = 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). Conclusions: 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.