Plasma proteome profiling combined with clinical and genetic features reveals the pathophysiological characteristics of β-thalassemia

Na Li; Peng An; Jifeng Wang; Tingting Zhang; Xiaoqing Qing; Bowen Wu; Lang Sun; Xiang Ding; Lili Niu; Zhensheng Xie; Mengmeng Zhang; Xiaojing Guo; Xiulan Chen; Tanxi Cai; Jianming Luo; Fudi Wang; Fuquan Yang

doi:10.1016/j.isci.2022.104091

Plasma proteome profiling combined with clinical and genetic features reveals the pathophysiological characteristics of β-thalassemia

iScience. 2022 Mar 16;25(4):104091. doi: 10.1016/j.isci.2022.104091. eCollection 2022 Apr 15.

Authors

Na Li^{1

2}, Peng An³, Jifeng Wang¹, Tingting Zhang^{1

2}, Xiaoqing Qing^{1

2}, Bowen Wu^{1

2}, Lang Sun^{1

2}, Xiang Ding¹, Lili Niu¹, Zhensheng Xie¹, Mengmeng Zhang¹, Xiaojing Guo^{1

2}, Xiulan Chen^{1

2}, Tanxi Cai^{1

2}, Jianming Luo⁴, Fudi Wang⁵, Fuquan Yang^{1

2}

Affiliations

¹ Key Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
⁴ Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021 China.
⁵ The Fourth Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou 310058 , China.

Abstract

The phenotype of β-thalassemia underlies multigene interactions, making clinical stratification complicated. An increasing number of genetic modifiers affecting the disease severity have been identified, but are still unable to meet the demand of precision diagnosis. Here, we systematically conducted a comparative plasma proteomic profiling on patients with β-thalassemia and healthy controls. Among 246 dysregulated proteins, 13 core protein signatures with excellent biomarker potential are proposed. The combination of proteome and patients' clinical data revealed patients with codons 41/42 -TTCT mutations have an elevated risk of higher iron burden, dysplasia, and osteoporosis than patients with other genotypes. Notably, 85 proteins correlating to fetal hemoglobin (Hb F) were identified, among which the abundance of 27 proteins may affect the transfusion burden in patients with β-thalassemia. The current study thus provides protein signatures as potential diagnostic biomarkers or therapeutic clues for β-thalassemia.

Keywords: Health sciences; Omics; Proteomics.