An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis
An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis
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DOI：
10.1073/pnas.0503178102
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发表时间：
2005-07-19
影响因子：
11.1
通讯作者：
Papini, AM
中科院分区：
文献类型：
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作者：
Lolli, F;Mulinacci, B;Papini, AM
多发性硬化症 (MS) 是一种复杂的疾病，似乎取决于多种病理生理过程。由于其不同的临床表现、自然史和对治疗干预的反应，多发性硬化症可以被认为是一组尚未被表征的疾病，从而导致难以评估预后。在过去的几年中，自身抗体在多发性硬化症中的作用得到了重新评估，因此，将其鉴定为特异性生物标志物成为相关目标。在本文中，我们证明异常的 N-葡萄糖基化是 MS 中 autoAb 识别的基本决定因素。因此，我们开发了 CSF114(Glc)，这是一种抗原探针，可准确测量患者血清中的 IgM 自体抗体，作为疾病生物标志物。 CSF114(Glc) 的相关性通过其临床应用以及与疾病活动性和预后的相关性得到证明。事实上，CSF114(Glc) 是一种基于结构设计的糖肽，能够通过 ELISA 识别 MS 患者群体血清中特定 IgM 自体抗体的存在，但不能识别献血者和其他自身免疫性疾病患者的血清中存在的特定 IgM 自体抗体。通过免疫组织化学，从多发性硬化症患者中分离出的针对 CSF114(Glc) 的特异性 AutoAb 可以识别髓磷脂和少突胶质细胞抗原，但不能识别其他不相关的组织。我们在一项针对未经治疗的多发性硬化症患者的纵向研究中证明，CSF114(Glc) 是一种可靠的特异性探针。 IgG/IgM 抗 CSF114(Glc) 抗体的发展与临床活动和 MRI 呈阳性的脑损伤平行。因此，基于 CSF114(Glc) 的血清免疫测定可能在监测多发性硬化症疾病进展、指导最佳治疗方面具有重要的预后价值。
Multiple sclerosis (MS) is a complex disease that seems to depend on several pathophysiological processes. Because of its varied clinical presentation, natural history, and response to therapeutic interventions, MS can be considered to be a group of diseases that have not been yet characterized, thus resulting in difficult evaluation of prognosis. in the last few years, the role of autoAbs in MS has been reevaluated, and, therefore, their identification as specific biomarkers became a relevant target. In this paper, we demonstrate that an aberrant N-glucosylation is a fundamental determinant of autoAb recognition in MS. Thus, we developed CSF114(Glc), an antigenic probe accurately measuring IgM autoAbs in the sera of a patient population, as disease biomarker. The relevance of CSF114(Glc) is demonstrated by its clinical application and correlation with disease activity and prognosis. In fact, CSF114(Glc), a structure-based designed glycopeptide, is able to recognize, by ELISA, the presence of specific IgM autoAbs in the sera of a MS patient population but not in blood donors and other autoimmune conditions. AutoAbs specific for CSF114(Glc) isolated from MS patients recognized myelin and oligodendrocyte antigens by immunohistochemistry but not other nonrelevant tissues. We demonstrate that CSF114(Glc) is a reliable, specific probe in a longitudinal study of untreated MS patients. Development of IgG/IgM anti-CSF114(Glc) Abs paralleled clinical activity and brain lesions positive to MRI. Therefore, a CSF114(Glc)-based immunoassay on sera may have important prognostic value in monitoring MS disease progression guiding optimal therapeutic treatment.