Hypomethylation and Overexpression of CD70 in CD4⁺ T Cells of the Patients with Immuno-Related Pancytopenia

Objective To study the expression of CD 70 and the methylation level of CD70 promoter in immuno-related pancytopenia (IRP) patients, and explore the role of CD70 in the pathogenesis of IRP.

Methods Thirty-five IRP patients and fifteen healthy donors were enrolled in this study. Peripheral blood mononuclear cells were isolated from venous blood by density gradient centrifugation and CD4⁺ T cells were isolated by immunomagnetic beads.The mRNA level and the percentage of CD70 of CD4⁺ T cells were measured by real-time quantitative polymerase chain reaction (RT-PCR) and flow cytometry respectively. Methylation-Specific PCR (MSP) was performed to determine the methylation level of CD70 promoter.

Results The percentage of CD70 expression on CD4⁺ T cells of untreated IRP patients[(7.46±1.51)%] was significantly higher than that of recovered IRP patients [(5.95±1.34) %] and normal controls [(1.83±0.6)%] and the result of recovered IRP patients was significantly higher than that of normal controls (P<0.05).The relative expressions of CD70 mRNA in CD4⁺ T cells were [2.314(0.200~6.084)]A[1.021 (0.135~3.434)]A [0.353 (0.008~2.258)] in three groups respectively. The differences between untreated IRP patients,recovered IRP patients and normal controls were significant (P<0.05). The CD70 promoter methylation level in CD4⁺ T cells of all IRP patients was significantly lower than that of normal controls (p<0.05). The expression of CD70 positively correlated to the ratio of CD5⁺ B cells (r=0.533, p<0.001).

Conclusions The overexpression of CD70 may lead to immunologic disarrangement and patients and it may play important role in the pathogenesis of IRP.