Abstract：
OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP.
METHODS: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells.
RESULTS: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients.
CONCLUSIONS: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.
METHODS: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells.
RESULTS: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients.
CONCLUSIONS: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.
摘要：
目的：慢性炎症性脱髓鞘性多发性神经病（CIDP）是一种周围神经自身免疫性疾病，其潜在病理生理学尚未完全了解。这项研究的重点是定义B和T细胞频率，CIDP患者的T细胞功能能力和先天免疫系统分析。
方法：通过使用多参数流式细胞术，我们检查了25CIDP患者的PBMC表型和功能，这些患者在符合EFNS/PNS标准的治疗中临床相对稳定，21例遗传证实为遗传性神经病变的患者和25例健康对照。我们还通过共培养Treg和效应T细胞来评估调节性T细胞(Treg)抑制能力。
结果：促炎性CD4T细胞，发现CI-DP患者的1型辅助性T细胞(Th1)和CD8T细胞产生炎性细胞因子的能力增强.CIDP患者与健康对照组中Th17调节细胞的频率没有差异，然而,DPCI患者Treg功能受损。先天免疫系统测量没有显着差异。在B细胞亚群中，CIDP患者的移行细胞频率降低。
结论：治疗后临床稳定的CI-DP患者继续显示出具有Treg功能受损的促炎状态的证据。这可能意味着不充分地抑制未通过标准的护理疗法解决的正在进行的炎症以及在治疗期间疾病的持续活动。靶向T细胞,特别是抑制Th1和多功能CD8T细胞或改善Treg细胞功能可能是未来治疗研究的潜在靶点。
方法：通过使用多参数流式细胞术，我们检查了25CIDP患者的PBMC表型和功能，这些患者在符合EFNS/PNS标准的治疗中临床相对稳定，21例遗传证实为遗传性神经病变的患者和25例健康对照。我们还通过共培养Treg和效应T细胞来评估调节性T细胞(Treg)抑制能力。
结果：促炎性CD4T细胞，发现CI-DP患者的1型辅助性T细胞(Th1)和CD8T细胞产生炎性细胞因子的能力增强.CIDP患者与健康对照组中Th17调节细胞的频率没有差异，然而,DPCI患者Treg功能受损。先天免疫系统测量没有显着差异。在B细胞亚群中，CIDP患者的移行细胞频率降低。
结论：治疗后临床稳定的CI-DP患者继续显示出具有Treg功能受损的促炎状态的证据。这可能意味着不充分地抑制未通过标准的护理疗法解决的正在进行的炎症以及在治疗期间疾病的持续活动。靶向T细胞,特别是抑制Th1和多功能CD8T细胞或改善Treg细胞功能可能是未来治疗研究的潜在靶点。
