【摘要】 【目的】探讨再生障碍性贫血(再障)儿童TCRVβ24个亚家族T细胞克隆性及其与HLA-DRB1*15的关系。【方法】再障儿童17例(SAA14例,MAA3例),采用RT-PCR和基因扫描分析外周血或骨髓TCRVβ24个亚家族基因的表达和克隆性,SSP-PCR检测HLA-DR。【结果】再障儿童外周血T细胞仅表达4～22个Vβ亚家族,而正常儿童外周血T细胞几乎表达所有Vβ亚家族。12例(包括初诊SAA4例,CR4例,复发1例和MAA3例)再障儿童存在不同程度T细胞克隆性增殖,但个体间差异较大,正常外周血和骨髓均为多克隆性T细胞。5例HLA-DRB1*15(+)患儿中4例(80%)有寡克隆T细胞,而12例HLA-DRB1*15(-)患儿中仅3例(25%)见寡克隆T细胞,两组比较差异具有显著意义(P<0.05)。伴寡克隆T细胞的6例SAA儿童经免疫抑制治疗后达CR;不伴寡克隆T细胞的5例SAA儿童接受免疫抑制治疗,其中CR1例,PR2例、无效1例,死亡1例。【结论】大多数再障儿童存在T细胞克隆性增殖,寡克隆T细胞多见于SAA,尤其是HLA-DRB1*15(+)的SAA儿童。TCRVβT细胞克隆的检测对进一步了解再障免疫功能状态、预测免疫抑制治疗效果具有一定的参考价值。更多还原

【Abstract】 [Objective] To investigate the expression pattern and clonality of TCR Vβ repertoire and its relationship to HLA-DRB1*15 genotype in children with aplastic anemia (AA). [Methods] The expressions of all the Vβ subfamily genes were evaluated by using RT-PCR and Vβ-CDR3 size distribution was analyzed by Genescan to determine the presence of Vβ subfamily clonal expansion in 17 pediatric AA patients. HLA-DRB1*15 was tested by SSP-PCR. [Results] Only 4-22 TCR Vβ subfamily genes were expressed in peripheral blood cells in AA patients while almost all of the Vβ subfamily genes were expressed in controls. Clonal expansion of T-cells was identified from 12 patients including 4 untreated severe AA, 4 complete remission, 1 relapse, and 3 moderate AA patients, but the Vβ subfamily of T- cell clones was different in each case. Oligoclonal T- cell was showed in four out of five patients bearing HLA-DRB1*15, while it was showed in 3 out of 12 patients with HLA-DRB1*15(-) (P< 0.05). Complete remission was resulted from immunosuppressive therapy in 6 patients with oligoclonal T-cell. Among the five patients without oligoclonal expansion of T cells, who accepted immunosuppressive therapy, one got complete remission, two partial remission, one unresponsive and the other died. [Conclusions] The majority of children with AA showed clonal expansion of T cells. Oligoclonal T-cells can be detected in severe AA patients, especially in those bearing HLA-DRB1*15. The analysis of clonality of TCR Vβ repertoire will be helpful to understand the immune pathological mechanism and predict the responsiveness to immunosuppressive treatment in AA.更多还原