Correlation between HLA-E*01∶03 positive genotype and acute leukemia

Abstract

Objective To analyze relationship between positive genotype of human leukocyte antigen(HLA)-E*01∶03 and acute leukemia (AL). Methods From January 2013 to December 2015, a total of 136 patients with AL who underwent blood group matching at Shenzhen Blood Center were included in this study as AL group. Among them, there were 78 male patients and 58 females; the age was (39±23) years. A simple random sampling method was used to select 182 health blood donors who participated in voluntary blood donation at the Shenzhen Blood Center in the same period. Among them, there were 101 male donors and 71 females; and age was (38±19) years. The sequence of exon 3 of HLA-E gene was determined by PCR-sequence based typing (SBT) method, and the genotype of HLA-E gene was determined. The peripheral blood lymphocytes from 54 patients in AL group and 64 healthy blood donors in control group were separated by density gradient centrifugation. The relative expressions of HLA-E on lymphocytes were detected by flow cytometry. The expression levels of plasma soluble HLA (sHLA)-E from 54 patients in AL group and 64 healthy blood donors in control group were detected by enzyme-linked immunosorbent assay (ELISA). The genotype frequencies of subjects in the two groups were compared by Chi-square test. The relative expression levels of HLA-E on peripheral blood lymphocytes and the expression level of sHLA-E in plasma were compared by independent samples t test, respectively. This study was in line with the procedures followed in this study were in accordance with the standards established by the Medical Ethics Committee of the Shenzhen Blood Center, and this study was approved by the committee (Approval No. SZBC-2017-007). All the subjects signed the informed consents for clinical trials and informed contents were obtained from all subjects. Results ① The genotype frequency of HLA-E*01∶03 positive genotype was 90.4% (123/136) of patients in AL group, which was higher than that of 77.5% (141/182) in control group, and the difference was statistically significant (χ2=9.286, P=0.002). ② Among the 54 patients in AL group and the 64 healthy blood donors in control group, the difference of relative expression levels of HLA-E on peripheral blood lymphocytes from subjects with HLA-E*01∶03 positive genotype between the two groups were not statistically significant [(3.3±0.4) vs (3.6±0.2); t=0.77, P=0.440]. The relative expression level of HLA-E on peripheral blood lymphocytes from patients with HLA-E*01∶03 negative genotype in AL group was (1.6±0.2), which was lower than that of (2.5 ± 0.2) in control group, and the difference was statistically significant (t=2.95, P=0.010). ③ Among 54 patients in AL group and 64 healthy blood donors in control group, the expression level of sHLA-E in plasma from patients with HLA-E*01∶03 positive genotype in AL group was (31.2±0.4 ) pg/mL, which was higher than that of (18.2±0.3) pg/mL in control group, and the difference was statistically significant (t=26.63, P<0.001). The expression level of sHLA-E in plasma from patients with HLA-E*01∶03 negative genotype in AL group was (32.9±1.3) pg/mL, which was lower than that of (18.8±0.8) pg/mL in the control group, and the difference was also statistically significant (t=8.89, P<0.001). Conclusions The HLA-E*01∶03 positive genotype frequency and the expression of sHLA-E in plasma have a certain correlation with AL. They may be a potential predictor and an auxiliary diagnostic indicator for AL. Key words: Leukemia, myeloid, acute; Leukemia, lymphoid; Genes, MHC class Ⅰ; Genotype; Human leukocyte antigen-E