Bidot Carlos J, Horstman Lawrence L, Jy Wenche, Jimenez Joaquin J, Bidot Carlos, Ahn Yeon S, Alexander J Steven, Gonzalez-Toledo Eduardo, Kelley Roger E, Minagar Alireza
Wallace H. Coulter Platelet Laboratory, University of Miami Dept. of Medicine, Miller School Of Medicine, Miami, FL, USA.
BMC Neurol. 2007 Oct 18;7:36. doi: 10.1186/1471-2377-7-36.
The presence of antiphospholipid antibodies (APLA) in multiple sclerosis (MS) patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA.
A consecutive cohort of 24 subjects with relapsing-remitting (RR) MS were studied of whom 7 were in remission (Rem) and 17 in exacerbation (Exc). All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL), beta2 glycoprotein I (beta2GPI), Factor VII/VIIa (FVIIa), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE).
In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p < 0.01, for all 6 target antigens. Interestingly, none of the MS patients had elevated plasma titers of IgG against any of the target antigens tested. Correlation analysis between MRI enhancing lesions and plasma levels of APLA revealed high correlation for aPC, aPS and aFVIIa (p </= 0.0065), a trend for aPE and aCL (p = 0.056), and no correlation for abeta2GP1. The strongest correlation was for aFVIIa, p = 0.0002.
The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.
多发性硬化症(MS)患者中抗磷脂抗体(APLA)的存在已被频繁报道,但迄今为止,APLA与MS的临床及神经影像学特征之间尚无明确关联。我们评估了血浆中存在APLA的MS患者的临床及神经影像学特征。
对24例复发缓解型(RR)MS患者进行连续队列研究,其中7例处于缓解期(Rem),17例处于加重期(Exc)。所有受试者均接受检查并进行脑部MRI检查。采用标准酶联免疫吸附测定法(ELISA)检测患者血浆中针对6种靶抗原的IgM和IgG抗体,这6种靶抗原分别为心磷脂(CL)、β2糖蛋白I(β2GPI)、因子VII/VIIa(FVIIa)、磷脂酰胆碱(PC)、磷脂酰丝氨酸(PS)和磷脂酰乙醇胺(PE)。
在加重期,高达80%的MS患者针对上述抗原的IgM抗体滴度升高。然而,在缓解期,不到一半的MS患者针对一种或多种上述抗原的IgM抗体滴度升高。对于所有6种靶抗原,这种差异具有显著性(p < 0.01)。有趣的是,没有MS患者针对所检测的任何靶抗原的IgG血浆滴度升高。MRI强化病灶与APLA血浆水平之间的相关性分析显示,抗磷脂酰胆碱(aPC)、抗磷脂酰丝氨酸(aPS)和抗因子VIIa(aFVIIa)之间存在高度相关性(p ≤ 0.0065),抗磷脂酰乙醇胺(aPE)和抗心磷脂(aCL)有相关趋势(p = 0.056),而与抗β2糖蛋白1(abeta2GP1)无相关性。相关性最强的是aFVIIa,p = 0.0002。
这项初步研究的结果表明,APLA IgM升高与MS的加重有关。目前,这种关联在MS发病机制中的意义尚不清楚。然而,需要进行系统的纵向研究,以测量更大队列的复发缓解型MS患者中的APLA,特别是在免疫调节药物治疗前后,以证实这些初步发现。