Jarius S, Eichhorn P, Franciotta D, Petereit H F, Akman-Demir G, Wick M, Wildemann B
Molecular Neuroimmunology Group, Department of Neurology, Otto Meyerhof Center, University of Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany.
Institute of Laboratory Medicine, Klinikum Großhadern, Ludwig Maximilian University, Munich, Germany.
J Neurol. 2017 Mar;264(3):453-466. doi: 10.1007/s00415-016-8360-4. Epub 2016 Dec 22.
It has long been known that the majority of patients with multiple sclerosis (MS) display an intrathecal, polyspecific humoral immune response to a broad panel of neurotropic viruses. This response has measles virus, rubella virus and varicella zoster virus as its most frequent constituents and is thus referred to as the MRZ reaction (MRZR).
Re-evaluation of the specificity of MRZR as a marker of MS.
Structured review of the existing English-, German- and Spanish-language literature on MRZR testing, with evaluation of MRZR in a cohort of 43 unselected patients with MS and other neurological diseases as a proof of principle.
A positive MRZ reaction, defined as a positive intrathecal response to at least two of the three viral agents, was found in 78% of MS patients but only in 3% of the controls (p < 0.00001), corresponding to specificity of 97%. Median antibody index values were significantly lower in non-MS patients (measles, p < 0.0001; rubella, p < 0.006; varicella zoster, p < 0.02). The 30 identified original studies on MRZR reported results from 1478 individual MRZR tests. A positive MRZR was reported for 458/724 (63.3%) tests in patients with MS but only for 19/754 (2.5%) tests in control patients (p < 0.000001), corresponding to cumulative specificity of 97.5% (CI 95% 96-98.4), cumulative sensitivity of 63.3% (CI 95% 59.6-66.8) (or 67.4% [CI 95% 63.5-71.1] in the adult MS subgroup), a positive likelihood ratio of 25.1 (CI 95% 16-39.3) and a negative likelihood ratio of 0.38 (CI 95% 0.34-0.41). Of particular note, MRZR was absent in 52/53 (98.1%) patients with neuromyelitis optica or MOG-IgG-positive encephalomyelitis, two important differential diagnoses of MS.
MRZR is the most specific laboratory marker of MS reported to date. If present, MRZR substantially increases the likelihood of the diagnosis of MS. Prospective and systematic studies on the diagnostic and prognostic impact of MRZR testing are highly warranted.
长期以来已知，大多数多发性硬化症（MS）患者对多种嗜神经病毒表现出鞘内多特异性体液免疫反应。这种反应以麻疹病毒、风疹病毒和水痘带状疱疹病毒为最常见成分，因此被称为MRZ反应（MRZR）。
重新评估MRZR作为MS标志物的特异性。
对现有关于MRZR检测的英文、德文和西班牙文文献进行结构化综述，并在一组43例未经选择的MS患者和其他神经系统疾病患者中评估MRZR，作为原理验证。
定义为对三种病毒制剂中至少两种呈鞘内阳性反应的阳性MRZ反应，在78%的MS患者中发现，但仅在3%的对照患者中发现（p<0.00001），特异性为97%。非MS患者的抗体指数中位数显著较低（麻疹，p<0.0001；风疹，p<0.006；水痘带状疱疹，p<0.02）。30项已确定的关于MRZR的原始研究报告了1478次个体MRZR检测的结果。MS患者中458/724（63.3%）的检测报告为阳性MRZR，但对照患者中仅19/754（2.5%）的检测报告为阳性（p<0.000001），累积特异性为97.5%（95%CI 96-98.4），累积敏感性为63.3%（95%CI 59.6-66.8）（成人MS亚组中为67.4%[95%CI 63.5-71.1]），阳性似然比为25.1（95%CI 16-39.
