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髓过氧化物酶-抗中性粒细胞胞质抗体相关性肾血管炎中 T 细胞受体使用的分析。

Analysis of T-cell receptor usage in myeloperoxidase--antineutrophil cytoplasmic antibody-associated renal vasculitis.

机构信息

Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Ibaraki, 300-0395, Japan,

出版信息

Clin Exp Nephrol. 2010 Feb;14(1):36-42. doi: 10.1007/s10157-009-0230-2. Epub 2009 Oct 7.

Abstract

BACKGROUND

Bacterial superantigens produced by Staphylococcus aureus may be associated with the onset of proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, including Wegener's granulomatosis. We investigated T-cell subsets to assess the superantigens present in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis.

METHODS

Peripheral-blood mononuclear cells (PBMC) obtained from 40 normal controls and ten patients with MPO-ANCA-associated vasculitis were stained with fluorescence-labeled monoclonal antibodies against T-cell markers, including 17 variable regions of T-cell receptor beta-chains (TCR-Vbeta) and were then analyzed using flow cytometry.

RESULTS

Among PBMCs, the percentage of CD3(+) cells from patients with MPO-ANCA-associated vasculitis was significantly lower than that from normal controls, but there were no differences between the two groups in the percentage of CD19(+) cells or CD16(+) cells. Although there were no differences regarding the overall percentage of CD4(+) cells between the two groups, the percentage of CD4(+)CD45RO(+) cells in patients with MPO-ANCA-associated vasculitis was significantly higher than that in normal controls, and percentages of CD4(+)CD45RO(+)HLA-DR(+) and CD4(+)CD45RO(+)CD62L(low) cells in patients with MPO-ANCA-associated vasculitis were also significantly increased. There was no significant difference between the two groups in terms of the usage of the 17 different TCR-Vbeta regions.

CONCLUSION

There was no difference in bacterial superantigens between controls and MPO-ANCA-associated vasculitis patients because of the absence of specific usage of TCR-Vbeta regions. Given the elevated levels of memory T cells, conventional antigens rather than superantigens may be associated with the pathogenesis of MPO-ANCA-associated vasculitis.

摘要

背景

金黄色葡萄球菌产生的细菌超抗原可能与蛋白酶 3 抗中性粒细胞胞质抗体(PR3-ANCA)相关血管炎有关,包括韦格纳肉芽肿。我们研究了 T 细胞亚群,以评估髓过氧化物酶-抗中性粒细胞胞质抗体(MPO-ANCA)相关血管炎患者中存在的超抗原。

方法

从 40 名正常对照者和 10 名 MPO-ANCA 相关血管炎患者中获得外周血单个核细胞(PBMC),并用针对 T 细胞标记物的荧光标记单克隆抗体进行染色,包括 T 细胞受体 β 链的 17 个可变区(TCR-Vbeta),然后使用流式细胞术进行分析。

结果

在 PBMC 中,MPO-ANCA 相关血管炎患者的 CD3(+)细胞百分比明显低于正常对照组,但两组之间 CD19(+)细胞或 CD16(+)细胞的百分比没有差异。虽然两组之间 CD4(+)细胞的总体百分比没有差异,但 MPO-ANCA 相关血管炎患者的 CD4(+)CD45RO(+)细胞的百分比明显高于正常对照组,而且 MPO-ANCA 相关血管炎患者的 CD4(+)CD45RO(+)HLA-DR(+)和 CD4(+)CD45RO(+)CD62L(low)细胞的百分比也明显增加。两组之间 17 个不同 TCR-Vbeta 区的使用没有显著差异。

结论

由于缺乏特定的 TCR-Vbeta 区使用,对照者和 MPO-ANCA 相关血管炎患者之间没有细菌超抗原的差异。鉴于记忆 T 细胞水平升高,与 MPO-ANCA 相关血管炎发病机制相关的可能是常规抗原而不是超抗原。

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