Format

Send to

Choose Destination
Sci Rep. 2018 Jul 9;8(1):10328. doi: 10.1038/s41598-018-28614-4.

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

Liu S1,2, Han J1,2, Gong H3, Li Y4, Bao X1, Qi J1, Liu H1,2, Chen J1,2, Wu X1,2, Xu Y1,3,2, Ma S5,6,7, Wu D8,9,10.

Author information

1
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
2
Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
3
Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, 215123, China.
4
Department of Rheumatology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.
5
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. mashoubao@suda.edu.cn.
6
Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, 215123, China. mashoubao@suda.edu.cn.
7
Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China. mashoubao@suda.edu.cn.
8
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. wudepei@medmail.com.cn.
9
Institute of Blood and Marrow Transplantation, Soochow University, Suzhou, 215123, China. wudepei@medmail.com.cn.
10
Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China. wudepei@medmail.com.cn.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center