Anticardiolipin, glutamic acid decarboxylase, and antinuclear antibodies in epileptic patients

Verrotti, Alberto; Greco, Rita; Altobelli, Emma; Latini, Giuseppe; Morgese, G; Chiarelli, Francesco

doi:10.1007/s102380300013

Cited by 18 publications

(23 citation statements)

References 33 publications

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“…In terms of GADA, contrasting results do exist. In a previous study, 2.1% of the patients with long‐standing drug‐resistant epilepsy had high GADA titers (Yoshimoto et al., 2005), but other reports did not observe significant differences in the prevalence of GADA between young patients with epilepsy and controls (Verrotti et al., 2003), or between patients with controlled and uncontrolled epilepsy (Kwan et al., 2000). In the prevalence studies, 1.4–5.4% of the patients had GADA titers similar to those we defined as low titers in our study (Kwan et al., 2000; Verrotti et al., 2003; Sokol et al., 2004; McKnight et al., 2005).…”

Section: Discussionmentioning

confidence: 85%

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

et al. 2010

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Summary Purpose: Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined. Methods: We analyzed GADA with a radioimmunoassay in sera of 253 well‐characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies. Results: GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [≥1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA‐positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra‐TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39–4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001). Discussion: High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.

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Section: Discussionmentioning

confidence: 85%

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

et al. 2010

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“…These frequencies are similar to what has been described in the literature. In contrast to the amount of data on the influence of aCL antibodies in seizures, [28][29][30] there are limited data on non-aCL antibodies as predictors; for example, anti-Smith antibodies have been correlated with disease activity and individual disease parameters, including organic brain syndrome and schizophrenia, [31][32][33][34] but not with seizures. Male gender and the presence of multiple NP manifestations were independent factors associated with the occurrence of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus

2005

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“…concluded in their study that the prevalence of aCL and ANA was higher in patients with epilepsy than in controls [44]. Yet, other studies suggest that aPL may contribute to epilepsy in some patients whose epilepsy is not their main disease: (a) Moderate to high titers of IgG aCL are associated with seizures in SLE patients [4,45,46]; (b) aCL obtained from patients with SLE who had seizures reduced the activity of inhibitory gamma-aminobutyric acid (GABA) receptors in snail neurons, suggesting a direct and reversible mechanism through which such Ab's might lower seizure threshold [47]; (c) aPL were found to depolarize brain nerve terminals, suggesting that such Ab's by themselves can be excitatory, and if so, this may provide a further basis for understanding the pathogenesis of epilepsy in APS [48]; (d) Immunization of mice with a monoclonal aCL resulted in APS with neurological dysfunction (including hyperactive behavior and impaired motor coordination) [49].…”

Section: Anti-glur3b Ab's In Epilepsymentioning

confidence: 93%

Antibodies to glutamate receptor subtype 3 (GluR3) are found in some patients suffering from epilepsy as the main disease, but not in patients whose epilepsy accompanies antiphospholipid syndrome or Sneddon's syndrome

et al. 2005

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Autoantibodies (Ab's) to the "B" peptide (amino acids 372-395) of glutamate/AMPA receptor subtype 3 (GluR3) are found in serum and cerebrospinal fluid of some patients with different types of epilepsy. Since such anti-GluR3B Ab's can activate and/or kill neurons in vitro and in vivo, they may contribute to epilepsy. To investigate whether anti-GluR3B Ab's may also be relevant to epilepsy when it accompanies some autoimmune-diseases, we tested for these Ab's in patients suffering from epilepsy that accompanies anti-phospholipid syndrome (APS) or Sneddon's syndrome (SNS), both being autoimmune-diseases with frequent neurological complications. We tested 77 pediatric patients whose epilepsy is their main disease; 31 adult patients whose epilepsy accompanies APS (primary or SLE-associated) or SNS; 45 epilepsy-free APS and SNS patients; and 90 healthy controls. Compared to the controls, significantly elevated anti-GluR3B Ab's were found in 22/77 (29%) patients whose epilepsy is their main disease, but in none of the patients whose seizures accompany APS or SNS. Yet, all the APS and SNS patients harbored the characteristic anti-phospholipid Ab's (aPL), directed against cardiolipin and beta2-glycoprotein I, and had lupus anti-coagulant. Thus, anti-GluR3B Ab's are not crossreactive with aPL, and not produced as a non-specific consequence of seizures on the one hand, or autoimmune-diseases on the other. Taken together with new findings accumulated recently in our lab, we suggest that anti-GluR3B Ab's are produced primarily in the periphery due to specific/non-specific "irritation" of the immune system, and that once they reach the brain via a leaky blood-brain barrier they may cause neuronal/glial damage and facilitate the outburst of epilepsy and additional neurological abnormalities. In contrast, the presence of anti-GluR3B Ab's does not seem to increase the probability of developing APS, SNS or the seizures that often accompany these autoimmune-diseases. These findings may have important diagnostic and therapeutic implications.

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Anticardiolipin, glutamic acid decarboxylase, and antinuclear antibodies in epileptic patients

Cited by 18 publications

References 33 publications

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

Factors at diagnosis predict subsequent occurrence of seizures in systemic lupus erythematosus

Antibodies to glutamate receptor subtype 3 (GluR3) are found in some patients suffering from epilepsy as the main disease, but not in patients whose epilepsy accompanies antiphospholipid syndrome or Sneddon's syndrome

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