Oligoclonal bands in multiple sclerosis cerebrospinal fluid: An update on methodology and clinical usefulness

Oligoclonal bands in multiple sclerosis cerebrospinal fluid: An update on methodology and clinical usefulness
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DOI:
10.1016/j.jneuroim.2006.07.006
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发表时间:
2006-11-01
影响因子:
3.3
通讯作者:
Huang, Yu-Min
Huang, Yu-Min
中科院分区:
医学4区
文献类型:
--
作者:
Link, Hans;Huang, Yu-Min

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通过分离脑脊液 (CSF) 蛋白检测到的两个或多个寡克隆 IgG 带 (OB),但在相应血清中未显示,反映了伴随中枢神经系统 (CNS) 炎症的局部 B 细胞反应。采用优化、标准化的方法,优先通过等电聚焦进行蛋白质分离,然后进行免疫印迹,超过 95% 的多发性硬化症 (MS) 患者血清中检测不到 IgG 类脑脊液 OB,从而为 MS 的诊断提供了有力的证据。一旦出现,无论 MS 病程或治疗如何,CSF OB 都会在个体患者中持续存在。由于 CSF OB 在 MS 中的高敏感性以及在适当的临床环境中的高特异性,强烈建议对 CSF 进行 IgG 类 OB 检查,以获得 MS 诊断的支持,并识别患有 MS 风险增加的临床孤立综合征 (CIS) 患者。 IgG 指数等于 CSF/血清 IgG:约 70% 的 MS 患者的 CSF/血清白蛋白升高,但在 CSF OB 阴性 MS 中很少见。由于诊断敏感性较低,在 MS 诊断中,不推荐 IgG 指数替代 CSF OB,但当其升高时,可作为中枢神经系统内 B 细胞反应增强的额外证据,与 MS 相容。尽管临床表现以及大脑和脊髓的磁共振成像结果对于多发性硬化症的诊断至关重要,但应在脑脊液 OB 阴性患者中重新评估,同时记住许多疾病实体与多发性硬化症相似。推荐的 MS 诊断标准必须包括腰椎穿刺作用的定义以及明确指定、优化和标准化的常规 CSF 检查(包括 CSF IgG OB 的存在)。需要对没有 CSF OB 的 MS 患者亚组进行协调一致的长期随访研究,例如:预后和免疫学特征。为了纳入疾病调节药物试验,建议根据是否存在 CSF OB 来选择 MS 或 CIS 患者。开发和评估新技术来定义 MS 或 CIS 患者与其他炎症性神经系统疾病患者的局部与全身 B 细胞反应,应该能够为 CSF OB 的作用提供新的线索,这一点仍然是个谜。 (c) 2006 Elsevier B.V. 保留所有权利。
Two or more oligoclonal IgG bands (OB) detected by separation of cerebrospinal fluid (CSF) proteins while not demonstrable in corresponding serum reflect a local B-cell response accompanying central nervous system (CNS) inflammation. Using optimized, standardized methodology, preferentially protein separation by isoelectric focusing followed by immunoblotting, more than 95% of patients with multiple sclerosis (MS) have CSF OB of IgG class not detectable in serum, thereby providing powerful evidence for the diagnosis of MS. Once present, CSF OB persists in the individual patient irrespective of MS course or therapy. Because of the high sensitivity of CSF OB in MS as well as its high specificity in the appropriate clinical setting, examination of CSF for OB of IgG class can be strongly recommended to obtain support for the diagnosis of MS and identify patients with clinically isolated syndrome (CIS) at increased risk of developing MS. The IgG index equal to CSF/serum IgG: CSF/serum albumin is elevated in about 70% of MS patients, but rarely in CSF OB-negative MS. Because of lower diagnostic sensitivity, IgG index cannot be recommended as replacement of CSF OB in the diagnosis of MS but, when elevated, as additional evidence for an augmented B-cell response within the CNS that is compatible with MS. Although the clinical picture as well as findings from magnetic resonance imaging of the brain and spinal cord are essential for an MS diagnosis, this should be re-evaluated in CSF OB-negative patients, keeping in mind the many disease entities imitating MS. Recommended diagnostic criteria for MS must include definitions of the role of lumbar puncture and of clearly specified, optimized and standardized routine CSF investigations including for the presence of CSF IgG OB. There is a need for concerted long-term follow-up studies of the subgroup of MS patients without CSF OB regarding e.g. prognostic and immunologic features. For inclusion in trials of disease-modulating drugs, it is recommended that patients with MS or CIS are selected regarding presence vs. absence of CSF OB. Development and evaluation of new technologies to define local vs. systemic B-cell responses in patients with MS or CIS vs. patients with other inflammatory neurological diseases should shed new light on the role of CSF OB, which remains enigmatic. (c) 2006 Elsevier B.V. All rights reserved.