Hüseyin Ali TÜNEL, Begüm Yavaşcaoğlu ÜNEY, İzzet HAFEZ, Endri BALLA, Arif Okay KARSLIOĞLU, Senem Has HASIRCI, Mediha Hacer ÜLGER, Elvin KESİMCİ, Bilkay BAŞTÜRK, Atila SEZGİN
Experimental and Clinical Transplantation - 2026;24(6):492-497
Objectives: Early prediction of graft rejection is critical for ensuring long-term graft survival and improving patient prognosis following heart transplant. Here, we investigated the association between interleukin 40, a proinflammatory cytokine, and key components of the innate (neutrophils) and adaptive (lymphocytes) immune systems. Furthermore, we evaluated the predictive value of the change in lymphocyte-to-neutrophil ratio for acute and chronic rejection and overall survival after heart transplant. Materials and Methods: In this 2-center study, peripheral blood lymphocyte and neutrophil counts were monitored in 121 heart transplant recipients at multiple time points: pretransplant, early postoperatively, and 1, 3, 6, 9, 12, 18, and 24 months posttransplant. Change in the lymphocyte-to-neutrophil ratio was calculated for each patient. Serum interleukin 40 levels were measured in patients with and without a confirmed diagnosis of rejection. We included a control group of 28 healthy volunteers. We performed statistical analyses to determine the relationship between change in lymphocyte-to-neutrophil ratio and acute rejection, chronic rejection, and patient survival. Results: Interleukin 40 levels and neutrophil percentages were significantly higher in the rejection group compared with the nonrejection and healthy control groups (P < .001). Conversely, lymphocyte percentage was significantly lower in the rejection group. Lymphocyte-to-neutrophil ratio was significantly different among study groups (P < .001). A negative correlation was identified between interleukin 40 levels and both lymphocyte percentage and lymphocyte-to-neutrophil ratio. Change in lymphocyte-to-neutrophil ratio demonstrated significant discriminatory power in predicting acute rejection (area under the curve = 0.631; P = .040), with lower rates of acute rejection observed in patients with a change in lymphocyte-to-neutrophil ratio of <=0.412. Correlation coefficients among hematological indices were robust and consistent with clinical findings. Conclusions: The significant correlation shown between interleukin 40 levels and lymphocyte-to-neutrophil ratio and rejection episodes in heart transplant recipients represents promising noninvasive biomarkers for predicting posttransplant rejection.
