重症肌无力患者外周血CD28^-T细胞亚群变化及临床意义

Changes of CD28^-T cell subsets and their clinical significance in myasthenia gravis patients

检测重症肌无力(MG)患者外周血CD28-T细胞亚群的变化,并探讨其临床意义。收集46例MG患者和35例健康对照(HC)外周血标本,采用免疫荧光染色和流式细胞术检测外周血CD4+CD28-和CD8+CD28-T细胞亚群。结果显示,MG患者和HC比较,前者CD28表达下调,CD4、CD8表达无差异;MG患者CD4+CD28-T细胞亚群(13.53%±6.31%)较HC(9.24%±4.62%)异常升高(P=0.001),而CD8+CD28-T细胞亚群(39.22%±11.91%)较HC(48.41%±13.63%)显著下降(P=0.002);全身型MG(GMG)和并发胸腺异常的MG患者中,CD4+CD28-T细胞亚群比例分别较眼肌型MG(OMG)和正常胸腺MG患者升高,而CD8+CD28-T细胞亚群百分比明显下降;QMGS评分与CD4+CD28-T细胞亚群呈正相关(r=0.4113,P=0.0045),而与CD8+CD28-T细胞亚群呈负相关(r=-0.3989,P=0.0060);激素治疗后伴随CD4+CD28-T细胞比例下降(P=0.018)和CD8+CD28-T细胞比例升高(P=0.018)。本研究发现,MG患者外周血CD4+CD28-T细胞亚群比例升高和CD8+CD28-T细胞亚群比例下降与疾病严重程度、治疗反应密切相关,且在不同临床分型的MG患者中存在差异性变化。上述提示CD28-T细胞亚群的异常变化可能参与了MG的免疫病理进程。

To investigate the clinical significance of CD28- T cell subsets in myasthenia gravis（MG） patients by analyzing theexpressions of CD4, CD8 and CD28 on peripheral blood lymphocytes, peripheral blood samples of 46 MG patients and 35 health controls（HC） were collected in our study. CD4, CD8 and CD28 expressed on lymphocytes were detected by flow cytometer. The results showed that there were no significant differences in CD4 and CD8 expressions on T lymphocytes between MG patients and HC. However, a decreased expression of CD28 was observed in MG patients. The percentage of CD4^＋ CD28- T cells in MG patients（ 13.53%± 6.31% ） was significantly higher than that in HC（9.24 %±4.62 %, P = 0. 001）, but a lower percentage of CD8^＋ CD28- T cells was found in MG patients （39.22 % ±11.91%） than that in HC （48.41%±13.63 %, P = 0. 002）. CD4^＋ CD28- T cell subset was enriched in GMG patients and MG patients complicated with abnormal thymus, while OMG patients and patients with normal thymus had an enrichment of CD8^＋ CD28- T cell subset. In addition, both CD4^＋ CD28- （r=0. 4113, P=0. 0045） and CD8^＋ CD28- （r=-0. 3989, P=0. 0060） T cell subsets were closely correlated to QMGS in MG patients. A decreased proportion of CD4^＋ CD28- T cells （P=0. 018） and an increased percentage of CD8^＋ CD28- T cells （P=0. 018） were found in MG patients on methylprednisolone therapy. Our study suggests that in MG patients there is an enrichment of CD4^＋ CD28- subset and a decline of CD8^＋ CD28 T cell subset, which is correlated to the severity of disease and corticosteroids therapy. In various clinical types of MG, significant differences between these two CD28- T cell subsets were observed, which indicated that changes of these two CD28 T cell subsets might be involved in the autoimmunity of MG.