MALDI-TOF-MS for Rapid Screening and Typing of β-Globin Variant and β-Thalassemia through Direct Measurements of Intact Globin Chains

作者：Zhang, Qianqian; Wang, Ge; Sun, Dehui; Lin, Wanying; Yan, Tizhen; Wu, Yuanjun; Wu, Meiying; Chen, Jianhong; Zou, Shaomin; Xie, Wenchun; Zhou, Yuqiu; Wang, Yuxi; He, Linlin; Liu, Yanhui; Qiu, Zhenxiong; Hu, Lingling; Lin, Bin; Zhou, Xiaoguang; Li, Yan^*; Xu, Xiangmin^*

来源：Clinical Chemistry, 2022, 68(12): 1541-1551.

DOI：10.1093/clinchem/hvac151

• MALDI-TOF
• hemoglobin disorders
• clinical investigation
• genetics
• hemoglobin

Background Traditional phenotype-based screening for beta-globin variant and beta-thalassemia using hematological parameters is time-consuming with low-resolution detection. Development of a MALDI-TOF-MS assay using alternative markers is needed. Methods We constructed a MALDI-TOF-MS-based approach for identifying various beta-globin disorders and classifying thalassemia major (TM) and thalassemia intermedia (TI) patients using 901 training samples with known HBB/HBA genotypes. We then validated the accuracy of population screening and clinical classification in 2 separate cohorts consisting of 16 172 participants and 201 beta-thalassemia patients. Traditional methods were used as controls. Genetic tests were considered the gold standard for testing positive specimens. Results We established a prediction model for identifying different forms of beta-globin disorders in a single MALDI-TOF-MS test based on delta- to beta-globin, gamma- to alpha-globin, gamma- to beta-globin ratios, and/or the abnormal globin-chain patterns. Our validation study yielded comparable results of clinical specificity (99.89% vs 99.71%), and accuracy (99.78% vs 99.16%) between the new assay and traditional methods but higher clinical sensitivity for the new method (97.52% vs 88.01%). The new assay identified 22 additional abnormal hemoglobins in 69 individuals including 9 novel ones, and accurately screened for 9 carriers of deletional hereditary persistence of fetal hemoglobin or delta beta-thalassemia. TM and TI were well classified in 178 samples out of 201 beta-thalassemia patients. Conclusions MALDI-TOF-MS is a highly accurate, predictive tool that could be suitable for large-scale screening and clinical classification of beta-globin disorders.

• 单位
  中国科学院; 南方医科大学; y; 中国科学院研究生院