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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-27R?) is a co-receptor of IL-27, an inflammatory cytokine that possesses extensive immunological functions. It has been reported that IL-27R? can exist in its soluble form (sIL-27R?) in human serum and can function as a natural IL-27 antagonist. In this study, we examined serum sIL-27R? 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-27R? at neutrophil engraftment was measured by ELISA. In the training set, a cut-off value of sIL-27R??=?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-27R? (?59.40?ng/ml) were significantly higher than those of patients with high serum sIL-27R? (<59.40?ng/ml). Multivariate analysis confirmed that low sIL-27R? level (HR?=?2.83 95% CI 1.29-6.19, P?

SUBMITTER: Liu S

PROVIDER: S-EPMC6037712 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Liu Shuangzhu S Han Jingjing J Gong Huanle H Li Yongsheng Y Bao Xiebing X Qi Jiaqian J Liu Hong H Chen Jia J Wu Xiaojin X Xu Yang Y Ma Shoubao S Wu Depei D

Scientific reports 20180709 1

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 ...[more]

PMID: 29985424

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Project description:Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor.

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

Publications

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

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