Garg Neeta, Zivadinov Robert, Ramanathan Murali, Vasiliu Irene, Locke Jaclyn, Watts Kelly, Lema Jordan, Rajeswary Jyotsna, Munschauer Frederick E, Ambrus Julian, Weinstock-Guttman Bianca
Multiple Sclerosis Center, UMass Memorial Medical Center, Worcester, MA 01605, USA.
J Neuroimmunol. 2007 Jul;187(1-2):159-65. doi: 10.1016/j.jneuroim.2007.04.008. Epub 2007 May 18.
Autoreactive antibodies (ARAB) occur more frequently in patients with multiple sclerosis (MS) than in general population and the presence of these antibodies often causes uncertainty regarding the disease course, response to therapy and the diagnosis of MS.
Retrospective analyses of the ARAB, clinical and MRI data of a consecutive patient cohort of MS and clinically isolated syndrome (CIS) patients were conducted. The patients were evaluated for an extensive panel that included various subtypes of antiphospholipid antibody (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti-SS-B antibodies. Quantitative MRI analysis was performed in a subgroup of MS patients measuring T2-lesion volume (LV), T1 black hole LV and brain parenchymal fraction (BPF).
A total of 137 patients (mean age 44.7, 84% female) with either MS (n=111; age: mean 46.5+/-S.D. 10.3 years; disease duration: mean 13.0+/-S.D. 10.4 years; EDSS: mean 3.2+/-S.D. 1.9) or CIS (n=26; age: mean 37.7+/-S.D. 7.8 years; disease duration: mean 1.3+/-S.D. 1.1 years; EDSS: mean 1.0+/-S.D. 0.7) were enrolled. Among MS patients, 82 were RRMS, 26 SPMS, and 3 had PPMS. Seventy-seven (69%) of MS patients showed presence of one or more ARAB. The proportion of MS patients with APLA was 55% (61 patients); IgM subtype was most frequent. Co-occurrence of ACA and APE was more frequent in SPMS as compared to RRMS (15.4% vs. 1.2%, p=0.012). The proportion of CIS patients with ARAB was 75% with IgM subtype being the most frequent. However, the ARAB in majority of CIS patients (9 out of 14, 64%) were transient on repeated testing. In a subgroup of 62 MS patients, quantitative MRI analysis showed significantly higher T2-LV in patients with positive APLA (15.1 ml for APLA positive vs. 6.75 ml for APLA negative) after correcting for the disease duration (p=0.048). The patients with ATA also had significantly higher T2-LV after correction for disease duration (19.0 ml vs.8.5, p=0.044).
ARAB were present in more than two thirds of MS and CIS patients although most of APLA in CIS were transient. The presence of APLA in MS patients was associated with higher T2-LV.
自身反应性抗体（ARAB）在多发性硬化症（MS）患者中出现的频率高于普通人群，这些抗体的存在常常导致对疾病进程、治疗反应以及MS诊断的不确定性。
对MS和临床孤立综合征（CIS）患者的连续队列中的ARAB、临床和MRI数据进行回顾性分析。对患者进行了广泛的检测，包括抗磷脂抗体（APLA）的各种亚型，如抗磷脂酰乙醇胺（APE）、抗磷脂酰丝氨酸（APS）、抗β2糖蛋白1（ABGP）、抗心磷脂（ACA），以及其他几种ARAB，如抗核抗体（ANA）、抗中性粒细胞胞浆抗体（ANCA）、抗甲状腺过氧化物酶抗体（ATA）、抗SS - A和抗SS - B抗体。对MS患者的一个亚组进行了定量MRI分析，测量T2病变体积（LV）、T1黑洞LV和脑实质分数（BPF）。
共纳入137例患者（平均年龄44.7岁，84%为女性），其中MS患者111例（年龄：平均46.5±标准差10.3岁；病程：平均13.0±标准差10.4年；扩展残疾状态量表（EDSS）：平均3.2±标准差1.9），CIS患者26例（年龄：平均37.7±标准差7.8岁；病程：平均1.3±标准差1.1年；EDSS：平均1.0±标准差0.7）。在MS患者中，82例为复发缓解型MS（RRMS），26例为继发进展型MS（SPMS），3例为原发进展型MS（PPMS）。77例（69%）MS患者显示存在一种或多种ARAB。MS患者中APLA的比例为55%（61例）；IgM亚型最为常见。与RRMS相比，SPMS中ACA和APE的共现更为频繁（15.4%对1.2%，p = 0.012）。CIS患者中ARAB的比例为75%，IgM亚型最为常见。然而，大多数CIS患者（14例中的9例，64%）的ARAB在重复检测时呈短暂性。在62例MS患者的亚组中，定量MRI分析显示，在校正病程后，APLA阳性患者的T2 - LV显著更高（APLA阳性患者为15.1 ml，APLA阴性患者为6.75 ml，p = 0.048）。校正病程后，ATA阳性患者的T2 - LV也显著更高（19.0 ml对8.5 ml，p = 0.044）。
超过三分之二的MS和CIS患者存在ARAB，尽管CIS中的大多数APLA是短暂性的。MS患者中APLA的存在与更高的T2 - LV相关。
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