Lymphocyte-to-Neutrophil Ratio and Interleukin-40 as Predictors of Rejection and Survival After Heart Transplantation.

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.