Model for the neuromuscular complications of systemic lupus erythematosus

Brey, Robin L.; Côté, Stephanie; Barohn, Richard; Jackson, Carlayne E.; Crawley, R R; Teale, Judy M.

doi:10.1177/096120339500400308

Cited by 24 publications

(7 citation statements)

References 12 publications

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“…Both passive and active immunization of normal laboratory mice with either aCL or with ␤2GP1 results in the induction of an experimental antiphospholipid antibody syndrome, including thrombocytopenia, placental infarction and fetal loss, MI, and neurological dysfunction. 38,39 In addition, mice with pinch-clamp injury to vascular endothelium develop a larger clot size with a longer time to dissolution when they are treated with human antiphospholipid antibody compared with control IgG. 40 Taken together, these studies provide important evidence that antiphospholipid antibodies can cause thrombosis and other antibody-mediated clinical manifestations.…”

Section: Discussionmentioning

confidence: 79%

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

Brey

Abbott

Curb

et al. 2001

Stroke

226

118

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Background-It has been hypothesized that immunoreactivity to ␤ 2 -glycoprotein 1 (␤2GP1)-dependent anticardiolipin antibody (aCL), but not ␤2GP1-independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). Methods-We performed a nested case-control study examining aCL as a risk factor for ischemic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured ␤2GP1-dependent and ␤2GP1-independent aCL and anti-␤2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI, and in a control group of 1360 men who remained free of both conditions. Results-Only ␤2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor-adjusted relative odds for men with a positive versus a negative ␤2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. Conclusions-These data suggest that aCL IgG, particularly the ␤2GP1-dependent variety, is an important predictor of future stroke and MI in men.

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Section: Discussionmentioning

confidence: 79%

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

Brey

Abbott

Curb

et al. 2001

Stroke

226

118

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“…In some of the models it has been shown that there are antibodies to neuronal tissue 22 and these animals are known to have CNS de®cits 23 ± 26 as well as peripheral neuromuscular dysfunction. 27 We have recently presented evidence supporting a speci®c role for aPL in mediating neurological and behavioral changes in animals in which high levels of aPL were induced by immunization with pathogenic monoclonal antibodies. 28 It is therefore relevant to examine the possibility that aPL mediate their effects by direct interaction with neuronal tissue.…”

Section: Introductionmentioning

confidence: 98%

Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes

Chapman

Cohen-Armon

Shoenfeld

et al. 1999

Lupus

175

121

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Antiphospholipid antibodies (aPL) are associated with neurological diseases such as stroke, migraine, epilepsy and dementia and are thus associated with both vascular and non-vascular neurological disease. We have therefore examined the possibility that these antibodies interact directly with neuronal tissue by studying the electrophysiological effects of aPL on a brain synaptosoneurosome preparation. IgG from patients with high levels of aPL and neurological involvement was purified by protein-G affinity chromatography as was control IgG pooled from ten sera with low levels of aPL. Synaptoneurosomes were purified from perfused rat brain stem. IgG from the patient with the highest level of aPL at a concentration equivalent to 1:5 serum dilution caused significant depolarization of the synaptoneurosomes as determined by accumulation of the lipophylic cation [3H]-tetraphenylphosphonium. IgG from this patient as well as IgG from two elderly patients with high levels of aPL were subsequently shown to permeabilize the synaptosomes to labeled nicotinamide adenine dinucleotide (NAD) and pertussis toxin-ADP-ribose transferase (PTX-A protein) as assayed by labeled ADP-ribosylation of G-proteins in the membranes. No such effects were seen with the control IgG. aPL may thus have the potential to disrupt neuronal function by direct action on nerve terminals. These results may explain some of the non-thromboembolic CNS manifestations of the antiphospholipid syndrome.

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“…9 Motor incoordination, reduced activity, and cognitive impairment have been described in MRL = lpr mice. 10,11 Recently, motor de cits and behavioral hyperactivity were described by our group in a mouse model induced by immunization with pathogenic monoclonal human anticardiolipin antibodies. 12 A model of APS, which is of special interest, is induced by immunization with b 2 -glycoprotein I (b 2 -GPI, also known as apolipoprotein H), which is a major cofactor in the binding of aPL.…”

Section: Introductionmentioning

confidence: 99%

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies

Shrot¹,

Katzav

Korczyn

et al. 2002

Lupus

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The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.

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Model for the neuromuscular complications of systemic lupus erythematosus

Cited by 24 publications

References 12 publications

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies

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Model for the neuromuscular complications of systemic lupus erythematosus

Cited by 24 publications

References 12 publications

β 2 -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

β 2 -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies

Contact Info

Product

Resources

About

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction

β ₂ -Glycoprotein 1–Dependent Anticardiolipin Antibodies and Risk of Ischemic Stroke and Myocardial Infarction