Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
J Neurol Sci. 2011 Jun 15;305(1-2):1-10. doi: 10.1016/j.jns.2011.03.026. Epub 2011 Apr 3.
As therapeutic options for multiple sclerosis widen, validated biomarkers of clinical disease activity are urgently needed. Reliable biomarkers would assist in choosing initial therapy, monitoring response to therapy, detecting subclinical disease activity, predicting and possibly preventing therapeutic failure, and hopefully improving both short (relapses) and long-term (disability) outcomes. The presence of oligoclonal bands in the cerebrospinal fluid is a well-validated biomarker that is useful in initial diagnosis. Neutralizing antibodies to interferon-beta are also useful in identifying treatment failure and possibly guiding changes in therapy. The discovery of antibodies to aquaporin-4 in patients with neuromyelitis optica delineates patients with a fundamentally different underlying pathophysiology and clinical course who may require alternate therapeutic approaches. While numerous other candidate biomarkers in serum and cerebrospinal fluid have been described, none so far have the validated reliability necessary for widespread clinical use. The availability of multiple genetic and protein microarray technology may assist in identifying more reliable candidate biomarkers or patterns of multiple biomarkers and improve specificity. The heterogeneity of multiple sclerosis may necessitate individualized biomarkers and therapeutic decisions within distinct subsets of patients.
随着多发性硬化症治疗选择的增多,迫切需要经过验证的临床疾病活动的生物标志物。可靠的生物标志物将有助于选择初始治疗、监测治疗反应、检测亚临床疾病活动、预测和可能预防治疗失败,并有望改善短期(复发)和长期(残疾)结局。脑脊液寡克隆带的存在是一种经过充分验证的生物标志物,可用于初始诊断。针对干扰素-β的中和抗体也有助于确定治疗失败,并可能指导治疗方案的改变。水通道蛋白-4 抗体在视神经脊髓炎患者中的发现,明确了具有根本不同潜在病理生理学和临床过程的患者,他们可能需要不同的治疗方法。尽管已经描述了许多其他候选血清和脑脊液生物标志物,但迄今为止,没有一种具有广泛临床应用所需的经过验证的可靠性。多种基因和蛋白质微阵列技术的出现可能有助于识别更可靠的候选生物标志物或多个生物标志物的模式,并提高特异性。多发性硬化症的异质性可能需要在不同患者亚群中进行个体化的生物标志物和治疗决策。