[show abstract][hide abstract] ABSTRACT: OBJECTIVES: This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. ORGANIZATION: After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. CONCLUSION: The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology.
Journal of Neuroinflammation 02/2009; 6:3. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glutamate is a major excitatory neurotransmitter in the central nervous system and plays a significant role in the pathophysiology of ischemic stroke. During acute ischemic cerebrovascular disease, glutamate efflux in the CNS produces excitotoxicity in neurons and may mediate forms of stress in other tissues expressing glutamate ionotropic (N-methyl-D-aspartate (NMDA)) receptors, e.g., cerebral endothelial cells. While endothelial cell stress in response to glutamate has been reported (oxidant stress, loss of barrier function), changes in protein expression produced by glutamate (an agonist of metabotropic and NMDA receptors) have not been documented. Here, we have examined how exposure of human cerebral endothelial cells to glutamate, in the presence and absence of the NMDA receptor antagonist MK-801, can alter the proteomic profile of cerebral endothelial cells. We found several important changes in the proteins expressed by cerebral endothelial cells in response to glutamate. Interestingly, MK-801 itself had some direct effects on cerebral endothelial cells. Taken together, our findings demonstrate that cerebral endothelial cells respond to glutamate by altering their protein expression profile. We assume that protein alterations found in the cerebral endothelial proteome, in response to glutamate and which were blocked by MK-801, may be important vascular targets in better understanding the pathogenesis of ischemic stroke.
Journal of Molecular Neuroscience 11/2008; 38(2):182-92. · 2.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our objective was to study a possible contribution of major histocompatibility complex (MHC) genes to soluble HLA-I synthesis in patients with systemic lupus erythematosus (SLE). Solid-phase enzyme-linked immunoassay (ELISA) was used to measure sHLA-I in the sera of 20 patients with SLE and 76 normal controls with known HLA phenotypes. Serial serum samples ( n=108) from the above group of patients ( n=19) were further investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Soluble HLA-I levels were abnormally higher in patients with SLE than normal controls ( P<0.0002). No complete HLA haplotype has been identified to be correlated with high or low sHLA-I secretion. Only the sera of HLA-A23- or -A24- (splits of HLA-A9) positive individuals were found to contain high sHLA-I concentrations in both populations studied. The difference between sHLA-I of HLA-A24 patients ( n=7) and HLA-A24 normal controls ( n=19) was statistically highly significant ( P<0.0079). The results suggest that HLA-A24 may confer additional risk of more severe disease expression in female patients with SLE. The data imply that SLE patients carrying 39-kDa sHLA-I have increased risk of developing renal disease. A higher prevalence of 35-37 kDa was observed in patients with mild disease. Interestingly, 44-46 kDa was the predominant molecular form of sHLA-I in SLE patients with lymphocytosis with no evidence of organ involvement. Notably, all these variations were not reflected by differences in HLA phenotypes, with the exception of HLA-A24-positive patients, in whom the 44-46-kDa form occurs consistently but not exclusively. In summary, the results show a genetic heterogeneity of SLE with MHC control of the expression of sHLA-I concentrations and possible involvement of disease-associated factors that might potentiate a specific sHLA-I molecule synthesis.
Rheumatology International 11/2003; 23(6):294-300. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Devic disease is characterized by an attack or attacks of optic neuritis and necrotizing myelitis without clinical or magnetic resonance imaging (MRI) evidence of brain involvement or presence of oligoclonal bands in the cerebrospinal fluid (CSF). More than a century after its first systematic study by the French physician, Eugene Devic, its cause as well as its pathogenesis, remains unknown. Devic disease is both a diagnostic and therapeutic challenge to clinicians. The authors present the latest review on the nature, course, possible mechanisms, and therapeutic options of Devic disease.