Soluble interleukin-27 receptor alpha is a valuable prognostic biomarker for acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Abstract

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication after allogeneic haematopoietic stem cell transplantation. Interleukin-27 receptor alpha (IL-27Rα) is a co-receptor of IL-27, an inflammatory cytokine that possesses extensive immunological functions. It has been reported that IL-27Rα can exist in its soluble form (sIL-27Rα) in human serum and can function as a natural IL-27 antagonist. In this study, we examined serum sIL-27Rα levels and evaluated their prognostic value in aGVHD. A total of 152 subjects were prospectively recruited and separated into the training group (n = 72) and the validation group (n = 80). Serum sIL-27Rα at neutrophil engraftment was measured by ELISA. In the training set, a cut-off value of sIL-27Rα = 59.40 ng/ml was identified to predict grade II–IV aGVHD (AUC = 0.735, 95% CI 0.618–0.853, P = 0.001). Cumulative incidences of grade II–IV aGVHD ( P = 0.004), relapse rate ( P = 0.008), and non-relapse mortality ( P = 0.008) in patients with low serum sIL-27Rα (≥59.40 ng/ml) were significantly higher than those of patients with high serum sIL-27Rα (<59.40 ng/ml). Multivariate analysis confirmed that low sIL-27Rα level (HR = 2.83 95% CI 1.29–6.19, P < 0.01) was an independent risk factor for predicting grade II-IV aGVHD. In addition, serum sIL-27Rα was positively correlated with IL-27 (R = 0.27, P = 0.029), IL-10 (R = 0.37, P = 0.0015) and HGF (R = 0.27, P = 0.0208), but was negatively correlated with TNFR1 (R = −0.365, P = 0.0022) and ST2 (R = −0.334, P = 0.0041), elafin (R = −0.29, P = 0.0117), and REG3α (R = −0.417, P = 0.0003). More importantly, the threshold value of sIL-27Rα was then validated in an independent cohort of 80 patients (AUC = 0.790, 95% CI 0.688–0.892, P < 0.001). Taken together, our findings suggested that serum sIL-27Rα at neutrophil engraftment maybe a valuable prognostic biomarker in predicting the incidence of moderate-to-severe aGVHD.