Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases.
Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases.
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DOI：
10.4049/jimmunol.1302884
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发表时间：
2014-03-15
期刊：
影响因子：
--
通讯作者：
Bielekova B
中科院分区：
文献类型：
--
作者：
Han S;Lin YC;Wu T;Salgado AD;Mexhitaj I;Wuest SC;Romm E;Ohayon J;Goldbach-Mansky R;Vanderver A;Marques A;Toro C;Williamson P;Cortese I;Bielekova B
我们对221名神经免疫学疾病诊断的受试者进行了无偏倚的、全面的脑脊液(CSF)和血白细胞免疫表型分析，以深入了解鞘内免疫反应的疾病特异性表型。对14个不同免疫细胞亚群的量化，以及对其激活状态的评估，揭示了鞘内免疫和全身免疫之间的生理差异，无论最终诊断如何。我们的数据与一个模型一致，在该模型中，中枢神经系统形成鞘内免疫反应，以提供有效的保护，防止持续性，特别是记忆T细胞、浆细胞样树突状细胞和CD56bright NK细胞。我们的数据还认为，脑脊液免疫细胞并不只是反映从外周招募的细胞。相反，它们代表了从血液中招募的细胞的混合物，这些细胞在鞘内被激活，并在执行效应器功能后离开中枢神经系统。诊断特异性差异提供了对多发性硬化症(MS)、新生儿发作性多系统炎症性疾病和Aicardi-Goutieres综合征亚型疾病过程的机械性洞察。这项分析还确定，与原发进展型多发性硬化症患者相比，继发性进展型多发性硬化症患者在免疫学上更接近复发缓解患者。由于脑脊液免疫表型分析捕捉到了鞘内炎症过程的生物学特征，因此有可能指导个别患者最佳选择免疫调节治疗并监测其疗效。我们的研究增加了越来越多的文献，证明了神经免疫性疾病患者全身炎症生物标志物和鞘内炎症生物标志物之间的相关性很差，并强调了直接在鞘内研究免疫反应的重要性。
We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders in order to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model, where the central nervous system shapes intrathecal immune responses to provide effective protection against persistent, especially by memory T cells, plasmacytoid dendritic cells and CD56bright NK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease and Aicardi-Goutieres syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared to patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0601335103
发表时间：
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影响因子：
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作者：
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影响因子：
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