Abstract
BackgroundThe 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.MethodsA 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), β2 glycoprotein I (β2GPI), Factor VII/VIIa (FVIIa), phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE).ResultsIn 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 aβ2GP1. The strongest correlation was for aFVIIa, p = 0.0002.ConclusionThe 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.
Highlights
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
Multiple sclerosis (MS) is an immune-mediated neurodegenerative disorder of human central nervous system, which is initially characterized by loss of myelin/oligodendrocyte complex followed by progressive neuronal loss and axonal degeneration [1,2,3]
The first such cofactor identified was β2 glycoprotein I (β2GPI), said to be associated with thrombosis, but many others were subsequently identified, numbering in the dozens. This discovery has greatly broadened the definition of APLA, and makes clear that APLA detected by standard ELISA methods are in reality very heterogeneous [14,15]
Summary
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. MS lesions within MS are characterized by perivenular infiltration of myelin basic protein-activated CD4 T lymphocytes as well as reactive macrophages which orchestrate the massive inflammatory cascade within the CNS [2] Another arm of the immune system, the humoral immune systemautoantibodies as well as activated complement systemalso play a significant role in the pathogenesis of MS [2,3]. A major advance was the realization that most APLA are directed not against phospholipids (PL) per se, but against PL-binding proteins [13] The first such cofactor identified was β2GPI, said to be associated with thrombosis, but many others were subsequently identified, numbering in the dozens. This discovery has greatly broadened the definition of APLA, and makes clear that APLA detected by standard ELISA methods are in reality very heterogeneous [14,15]
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