Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression

Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression
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DOI:
10.1016/s0165-5728(03)00221-2
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发表时间:
2003-08-01
影响因子:
3.3
通讯作者:
Pelfrey, CM
Pelfrey, CM
中科院分区:
医学4区
文献类型:
--
作者:
Moldovan, IR;Rudick, RA;Pelfrey, CM

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髓磷脂抗原的自身反应性与多发性硬化症 (MS) 疾病进展之间的关系尚不完全清楚。我们通过横断面比较多发性硬化症残疾的客观指标和免疫细胞因子对髓磷脂蛋白的反应来解决这种关系。 ELISPOT 测定用于测定 20 名复发缓解型 (RR) MS 患者和 27 名年龄和年龄组患者的外周血单核细胞 (PBMC) 响应跨越整个蛋白脂质蛋白 (PLP) 和髓鞘碱性蛋白 (MBP) 分子的肽而产生的体外干扰素 γ (IFN-γ) 和白细胞介素 10 (IL-10)。 性别匹配的健康对照。与健康对照相比,MS 患者表现出显着更高的 MBP 诱导的 IFN-γ 反应和 PLP 诱导的 IL-10 反应。使用多发性硬化症功能复合物 (MSFC)(一种新的多因素残疾测量方法),MS 患者显示出对 PLP 肽和 MBP 肽的 IFNγ 反应与残疾之间存在显着相关性。相反,在多发性硬化症患者中,MSFC 与对无关对照抗原或有丝分裂原的反应之间没有相关性。这些数据表明,分泌炎性细胞因子 IFNγ 的髓磷脂特异性 T 淋巴细胞与 MS 的功能损伤相关,支持髓磷脂免疫反应与 MS 残疾之间存在抗原特异性联系。 (C) 2003 Elsevier B.V. 保留所有权利。
The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFN-gamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls. MS patients showed significantly higher MBP-induced IFN-gamma responses and PLP-induced IL-10 responses compared with healthy controls. Using the Multiple Sclerosis Functional Composite (MSFC), a new multifactorial measure of disability, MS patients showed a significant correlation between the IFNgamma response to PLP peptides and MBP peptides, and disability. In contrast, in MS patients, there was no correlation between the MSFC and the response to unrelated control antigens or mitogens. These data show that myelin-specific T lymphocytes secreting the inflammatory cytokine IFNgamma correlate with functional impairment in MS, supporting an antigen-specific link between the immune response to myelin and disability in MS. (C) 2003 Elsevier B.V. All rights reserved.