2022, Vol. 26 ›› Issue (31): 5032-5039

Correlation of the level of plasma biomarkers with acute graft-versus-host disease in children

Wen Jianyun1, Miao Lili2, Guan Di2, Liu Xuan1, Chen Libai1, Feng Xiaoqin1, Xu Xiaoxiao1, Liu Qiujun1, Wu Xuedong1, He Yuelin1   

Abstract: BACKGROUND: Acute graft-versus-host disease is one of the major complications of allogeneic hematopoietic stem cell transplantation, and it is also the key to the success of transplantation, which is particularly important to find specific biomarkers of acute graft-versus-host disease for the early diagnosis and treatment. The immune function of children is imperfect, and the changes of plasma biomarkers after acute graft-versus-host disease have their own characteristics.  
OBJECTIVE: To explore the correlation of plasma levels of soluble growth stimulation expressed gene 2 (sST2), regenerating islet-derived protein 3 alpha (REG3α), tumor necrosis factor receptor 1 (TNFR1), interleukin 6 (IL6), and interleukin 8 (IL8) with acute graft-versus-host disease in children after allogeneic hematopoietic stem cell transplantation. It is expected to provide reliable detection biomarkers for early diagnosis of acute graft-versus-host disease and prediction of therapy effect and prognosis.
METHODS: Samples were collected from 127 pediatric patients who underwent allogeneic hematopoietic stem cell transplantation from March 2019 to December 2020 in the Department of Pediatrics, Nanfang Hospital. The plasma was collected at multiple time points, including 10 days before transplantation, 0, 7, 14, 28, and 90 days after transplantation, at the onset of acute graft-versus-host disease symptoms, 1, 2, and 4 weeks after acute graft-versus-host disease therapy. The plasma concentrations of sST2, REG3α, TNFR1, IL6 and IL8 were detected by the Luminex technology.  
RESULTS AND CONCLUSION: (1) Plasma samples were collected from 100 of 127 patients at the point of occurrence of acute graft-versus-host disease. Sixty cases never developed acute graft-versus-host disease symptoms; 40 cases presented acute graft-versus-host disease, among which 9 cases developed II-IV gastrointestinal acute graft-versus-host disease according to EBMT-NIH-CIBMTR classification standard. (2) The plasma concentrations of sST2 and REG3α at onset point in patients were significantly higher in the acute graft-versus-host disease group compared with the non-acute graft-versus-host disease group (P < 0.05). sST2 was significantly increased at 7 days after transplantation in the acute graft-versus-host disease group than that in the non-acute graft-versus-host disease group (P < 0.05). The sST2 and REG3α levels were significantly higher in the II-IV gastrointestinal acute graft-versus-host disease group than those in the non-gastrointestinal acute graft-versus-host disease group (P < 0.01; P < 0.05). There were no significant differences in TNFR1, IL6 and IL8 levels at onset point and 7 days after transplantation in patients between the acute graft-versus-host disease group and the non-acute graft-versus-host disease group (P > 0.05). (3) In all acute graft-versus-host disease patients, the plasma concentrations of sST2 and REG3α in the steroid-resistant acute graft-versus-host disease group showed increasing tendency compared with steroid-sensitive acute graft-versus-host disease group. (4) It is concluded that the increate of plasma sST2 and REG3α levels at onset point after transplantation suggests the incidence of acute graft-versus-host disease. sST2 and REG3α in plasma can be helpful for the early prediction of acute graft-versus-host disease. By analyzing the levels of biomarkers at 1, 2, and 4 weeks after treatment, no decrease in the sST2 and REG3α levels in patients with acute graft-versus-host disease after treatment may be related to poor prognosis.
Key words: acute graft-versus-host disease, plasma biomarkers, allogeneic hematopoietic stem cell transplantation, soluble growth stimulation expressed gene 2, regenerating islet-derived protein 3 alpha