Recovery of the T-cell repertoire in CIDP by IV immunoglobulins

Recovery of the T-cell repertoire in CIDP by IV immunoglobulins
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DOI:
10.1212/wnl.0b013e31827debad
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发表时间:
2013-01-01
期刊:
影响因子:
9.9
通讯作者:
Kieseier, Bernd C.
Kieseier, Bernd C.
中科院分区:
医学1区
文献类型:
--
作者:
Mausberg, Anne K.;Dorok, Mareike;Kieseier, Bernd C.

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目的:探讨慢性炎症性脱髓鞘性多发性神经病 (CIDP) 患者未接受或接受静脉注射免疫球蛋白 (IVIg) 治疗时 T 细胞库的变化。方法:采用 CDR3 谱型分析外周血中 CD4+ 和 CD8+ T 细胞的 T 细胞受体 (TCR) 库。 CIDP 患者包括未接受 IVIg 治疗 (n = 14) 和接受 IVIg 治疗 (n = 11) 的横断面和纵向 (n = 2)。 结果:虽然 CIDP 患者的 TCR 长度分布对于 CD4+ T 细胞的大多数 V β 元件仅发生适度改变,但 CD8+ 群体在所有分析的 24 V β 元件中显示出广泛的寡克隆扩增。在大多数受影响的患者中,未检测到一种 V β 元件的明显 TCR 长度的公开扩展。 IVIg 治疗减少了 CD4+ 和 CD8+ 群体内的寡克隆扩增。结论:我们的数据表明,细胞毒性 CD8+ T 细胞表现出比 CD4+ T 细胞更广泛的激活,表明 CD8+ T 细胞在 CIDP 免疫发病机制中具有潜在的关键作用。 T 细胞激活中深刻的寡克隆反应表明多种肽可能诱导和传播这种自身免疫驱动的疾病。观察到的高度活化的 T 细胞减少可能有助于 IVIg 的治疗效果。神经病学(R)2013;80:296-303
Objective: To investigate changes in the T-cell repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) without and with treatment of IV immunoglobulins (IVIg).Methods: The T-cell receptor (TCR) repertoire of CD4+ and CD8+ T cells in the peripheral blood was analyzed using CDR3 spectratyping. Patients with CIDP were included without (n = 14) and with IVIg treatment (n = 11) cross-sectionally and longitudinally (n = 2).Results: While the TCR length distribution of patients with CIDP was only moderately altered for most of the V beta elements of CD4+ T cells, the CD8+ population displayed extensive oligoclonal expansions in all analyzed 24 V beta elements. A public expansion of a distinct TCR length in one V beta element within a majority of affected patients was not detectable. Treatment with IVIg reduced the oligoclonal expansions within both the CD4+ and CD8+ population.Conclusions: Our data demonstrate that cytotoxic CD8+ T cells exhibit a much broader activation than CD4+ T cells, indicating a potentially crucial role of CD8+ T cells in the immunopathogenesis of CIDP. The profound oligoclonal response in T-cell activation suggests that multiple peptides may induce and propagate this autoimmune-driven disease. The observed reduction of highly activated T cells may contribute to the therapeutic effects of IVIg. Neurology (R) 2013;80:296-303