GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies
Abstract Background Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmu...
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doaj-eaf74a388fd64ccfaa98583de32cf6bb2020-11-24T21:47:41ZengBMCOrphanet Journal of Rare Diseases1750-11722018-04-011311910.1186/s13023-018-0787-5GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologiesSuvi Liimatainen0Jerome Honnorat1Sean J. Pittock2Andrew McKeon3Mario Manto4Jared R. Radtke5T1D Exchange BiobankChristiane S. Hampe6Department of Neurology and Rehabilitation, Tampere University HospitalUniversity of Lyon - University Claude Bernard LyonDepartment of Neurology, College of Medicine, Mayo ClinicDepartment of Neurology, College of Medicine, Mayo ClinicUnité d’Etude du Mouvement, Université Libre De BruxellesDepartment of Medicine, School of Medicine, University of WashingtonDepartment of Medicine, School of Medicine, University of WashingtonAbstract Background Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42). Results GAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients. Conclusions Different autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition.http://link.springer.com/article/10.1186/s13023-018-0787-5Autoimmune epilepsyType 1 diabetesGAD65AbEpitope mappingGAD65 enzyme activity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Suvi Liimatainen Jerome Honnorat Sean J. Pittock Andrew McKeon Mario Manto Jared R. Radtke T1D Exchange Biobank Christiane S. Hampe |
spellingShingle |
Suvi Liimatainen Jerome Honnorat Sean J. Pittock Andrew McKeon Mario Manto Jared R. Radtke T1D Exchange Biobank Christiane S. Hampe GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies Orphanet Journal of Rare Diseases Autoimmune epilepsy Type 1 diabetes GAD65Ab Epitope mapping GAD65 enzyme activity |
author_facet |
Suvi Liimatainen Jerome Honnorat Sean J. Pittock Andrew McKeon Mario Manto Jared R. Radtke T1D Exchange Biobank Christiane S. Hampe |
author_sort |
Suvi Liimatainen |
title |
GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
title_short |
GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
title_full |
GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
title_fullStr |
GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
title_full_unstemmed |
GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
title_sort |
gad65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2018-04-01 |
description |
Abstract Background Autoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42). Results GAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients. Conclusions Different autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition. |
topic |
Autoimmune epilepsy Type 1 diabetes GAD65Ab Epitope mapping GAD65 enzyme activity |
url |
http://link.springer.com/article/10.1186/s13023-018-0787-5 |
work_keys_str_mv |
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