Jarius S, Wilken D, Haas J, Ruprecht K, Komorowski L, Wildemann B
Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Euroimmun AG, Luebeck, Germany.
J Neurol. 2021 Oct;268(10):3758-3765. doi: 10.1007/s00415-021-10471-3. Epub 2021 Mar 26.
A positive MRZ reaction, as defined by intrathecal IgG production against at least two of its constituents, measles virus (M), rubella virus (R) and varicella zoster virus (Z), is detectable in ~ 63% of patients with multiple sclerosis (MS) and is currently considered the laboratory marker with the highest specificity and positive likelihood ratio for MS. However, M, R and Z are only the most well-established constituents of a broader intrathecal humoral immune response in MS.
To identify additional anti-microbial antibodies inclusion of which in the classical MRZ panel may result in increased sensitivity without compromising the marker's high specificity for MS.
We determined the antibody indices (AIs) for 11 viral and bacterial agents (M, R, Z, herpes simplex virus, Epstein-Barr virus, mumps virus, cytomegalovirus, parvovirus B19, Bordetella pertussis, Corynebacterium diphtheriae, and Clostridium tetani) in paired cerebrospinal fluid and serum samples from patients with MS and disease controls.
A positive 'classical' MRZ reaction was found in 17/26 (65.4%) MS patients. The five most frequently positive AIs among patients with MS were M (76.9%), Z (61.5%), R (57.7%), parvovirus B19 (42.3%), and mumps (28%). Addition of parvovirus B19 and mumps virus to the MRZ panel resulted in an increase in sensitivity in the MS group from 65.4% to 73.1%, with 22% of the initially MRZ-negative patients exhibiting a de novo-positive response. The extended MRZ panel ('MRZplus') distinguished sharply between MS (≥ 3 AIs in 90% of all positives) and controls (varying diagnoses, from migraine to vasculitis; 0-1 AIs; p < 0.000001). The highest median AI in the MS group was found for parvovirus B19 (3.97), followed by measles virus (2.79).
Inclusion of parvovirus B19 and mumps virus in the test panel resulted in an increase in the sensitivity and discriminatory power of MRZ. Our results provide a strong rational for prospective studies investigating the role of extended MRZ panels in the differential diagnosis of MS.
如针对其至少两种成分（麻疹病毒（M）、风疹病毒（R）和水痘带状疱疹病毒（Z））鞘内产生IgG所定义的阳性MRZ反应，在约63%的多发性硬化症（MS）患者中可检测到，目前被认为是MS特异性最高和阳性似然比最高的实验室标志物。然而，M、R和Z只是MS中更广泛的鞘内体液免疫反应中最知名的成分。
确定将其他抗微生物抗体纳入经典MRZ检测组是否可提高敏感性，同时又不影响该标志物对MS的高特异性。
我们测定了来自MS患者和疾病对照的配对脑脊液和血清样本中11种病毒和细菌制剂（M、R、Z、单纯疱疹病毒、EB病毒、腮腺炎病毒、巨细胞病毒、细小病毒B19、百日咳博德特氏菌、白喉棒状杆菌和破伤风梭菌）的抗体指数（AI）。
在17/26（65.4%）的MS患者中发现了阳性“经典”MRZ反应。MS患者中最常呈阳性的五个AI分别是M（76.9%）、Z（61.5%）、R（57.7%）、细小病毒B19（42.3%）和腮腺炎（28%）。将细小病毒B19和腮腺炎病毒添加到MRZ检测组中，使MS组的敏感性从65.4%提高到73.1%，最初MRZ阴性的患者中有22%出现了新的阳性反应。扩展的MRZ检测组（“MRZplus”）在MS（所有阳性中90%≥3个AI）和对照组（从偏头痛到血管炎的各种诊断；0 - 1个AI；p＜0.000001）之间有明显区分。MS组中AI中位数最高的是细小病毒B19（3.97），其次是麻疹病毒（2.79）。
在检测组中纳入细小病毒B19和腮腺炎病毒可提高MRZ的敏感性和鉴别能力。我们的结果为前瞻性研究扩展MRZ检测组在MS鉴别诊断中的作用提供了有力依据。
