Berger Thomas, Rubner Paul, Schautzer Franz, Egg Robert, Ulmer Hanno, Mayringer Irmgard, Dilitz Erika, Deisenhammer Florian, Reindl Markus
Department of Neurology, University of Innsbruck, Innsbruck, Austria.
N Engl J Med. 2003 Jul 10;349(2):139-45. doi: 10.1056/NEJMoa022328.
Most patients with multiple sclerosis initially present with a clinically isolated syndrome. Despite the fact that clinically definite multiple sclerosis will develop in up to 80 percent of these patients, the course of the disease is unpredictable at its onset and requires long-term observation or repeated magnetic resonance imaging (MRI). We investigated whether the presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite multiple sclerosis.
A total of 103 patients with a clinically isolated syndrome, positive findings on cerebral MRI, and oligoclonal bands in the cerebrospinal fluid were studied. At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. Neurologic examinations for relapse or disease progression (defined as conversion to clinically definite multiple sclerosis) were performed at base line and subsequently every three months.
Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than patients without these antibodies. Only 9 of 39 antibody-seronegative patients (23 percent) had a relapse, and the mean (+/-SD) time to relapse was 45.1+/-13.7 months. In contrast, 21 of 22 patients (95 percent) with antibodies against both MOG and MBP had a relapse within a mean of 7.5+/-4.4 months, and 35 of 42 patients (83 percent) with only anti-MOG antibodies had a relapse within 14.6+/-9.6 months (P<0.001 for both comparisons with antibody-seronegative patients). The adjusted hazard ratio for the development of clinically definite multiple sclerosis was 76.5 (95 percent confidence interval, 20.6 to 284.6) among the patients who were seropositive for both antibodies and 31.6 (95 percent confidence interval, 9.5 to 104.5) among the patients who were seropositive only for anti-MOG antibodies, as compared with the seronegative patients.
Analysis of antibodies against MOG and MBP in patients with a clinically isolated syndrome is a rapid, inexpensive, and precise method for the prediction of early conversion to clinically definite multiple sclerosis. This finding may be important for the counseling and care of patients with a first demyelinating event suggestive of multiple sclerosis.
大多数多发性硬化症患者最初表现为临床孤立综合征。尽管高达80%的此类患者会发展为临床确诊的多发性硬化症,但疾病在发病时的病程是不可预测的,需要长期观察或重复进行磁共振成像(MRI)检查。我们调查了临床孤立综合征患者血清中抗髓鞘少突胶质细胞糖蛋白(MOG)和髓鞘碱性蛋白(MBP)抗体的存在是否能预测转化为临床确诊多发性硬化症的时间间隔。
共研究了103例患有临床孤立综合征、脑MRI检查有阳性发现且脑脊液中有寡克隆带的患者。在基线时,采集血清样本,采用蛋白质印迹分析检测抗MOG和抗MBP抗体,并对脑MRI检测到的病变进行定量分析。在基线时及随后每三个月进行一次神经系统检查,以确定是否复发或疾病进展(定义为转化为临床确诊的多发性硬化症)。
与没有这些抗体的患者相比,抗MOG和抗MBP抗体阳性的患者复发更频繁且更早。39例抗体血清阴性患者中只有9例(23%)复发,复发的平均(±标准差)时间为45.1±13.7个月。相比之下,22例同时具有抗MOG和抗MBP抗体的患者中有21例(95%)在平均7.5±4.4个月内复发,42例仅具有抗MOG抗体的患者中有35例(83%)在14.6±9.6个月内复发(与抗体血清阴性患者的两项比较P均<0.001)。与血清阴性患者相比,两种抗体血清阳性的患者发生临床确诊多发性硬化症的调整后风险比为76.5(95%置信区间为20.6至284.6),仅抗MOG抗体血清阳性的患者为31.6(95%置信区间为9.5至104.5)。
对临床孤立综合征患者的抗MOG和抗MBP抗体进行分析,是预测早期转化为临床确诊多发性硬化症的一种快速、廉价且精确的方法。这一发现对于对首次出现提示多发性硬化症的脱髓鞘事件的患者进行咨询和护理可能具有重要意义。