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Autoantibodies to glutamic acid decarboxylase in patients with epilepsy and their relationship with type 1 diabetes: a pilot study
  1. Teresa C Moloney1,
  2. Iskandar Idris2,
  3. Patrick Waters1,
  4. Stephen Howell3,
  5. Angela Vincent1,
  6. Bethan Lang1,
  7. Paul Maddison4
  1. 1Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK
  2. 2Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Nottingham, UK
  3. 3Department of Clinical Neurology, Royal Hallamshire Hospital, Sheffield, UK
  4. 4Department of Clinical Neurology, Queen's Medical Centre, Nottingham, UK
  1. Correspondence to Dr Bethan Lang, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX3 9DS, UK; bethan.lang{at}ndcn.ox.ac.uk

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Introduction

Epilepsy is one of the most frequent neurological disorders affecting between 0.5% and 1% of the population, but in many the aetiology is unknown. A recent population-based study reported a fivefold increase in patients with type 1 diabetes mellitus (T1DM).1 Autoantibodies that recognise neuronal proteins have been identified in a number of immunotherapy-responsive seizure-related neurological disorders.2 High-titre autoantibodies to glutamic acid decarboxylase (GAD), an intracellular enzyme that catalyses the synthesis of gamma-aminobutyric acid (GABA) have been detected in neurological diseases including epilepsy although these patients show a less clear response to immunotherapies.3 ,4 GAD is also expressed by pancreatic β cells and is a major autoantigen in T1DM. Antibodies to GAD (GAD Abs) are present in up to 80% of patients with newly diagnosed T1DM, although not considered causative. There have been studies examining the incidence of GAD Abs in patients with epilepsy;5 however, we compare GAD and other Abs in patients with T1DM, with and without epilepsy.

Methods

Study design and participants

We recruited patients with T1DM (n=25) and coexistent epilepsy (T1DM/Ep) and sex-matched/age-matched patients with T1DM (n=36) from Nottingham and Sheffield Teaching Hospitals NHS Trust; the diagnoses of epilepsy and T1DM were established by specialist neurology (PM and SH) and diabetology (II) teams. Ethics approval was obtained, and written informed consent was obtained from all patients involved.

Radioimmunoassays

Voltage-gated potassium channel (VGKC)-complex antibodies were determined by immunoprecipitation of 125I-α-dendrotoxin-labelled VGKC complexes from rabbit brain extract (positive >100 pmoles/L).5 GAD65 Abs were measured using …

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Footnotes

  • Contributors II, BL and PM conceived and designed the study. II is the guarantor to the study. II, PM and SH have provided patient material. TCM, PW and BL carried out the laboratory work. TCM, AV, PM and BL conducted the assessment of data and the analysis. All authors were involved in the coordination of the study, read, contributed towards and approved the final manuscript.

  • Funding Diabetes UK (II), Epilepsy Research UK (TCM and BL). NIHR Oxford Biomedical Research Centre.

  • Competing interests AV and the Nuffield Department of Clinical Neurosciences in Oxford receive royalties and payments for antibody assays and AV is the named inventor on patent application WO/2010/046716 entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. PW and BL are coinventors and have received royalties. PW has received speaker honoraria from Biogen Idec and Euroimmun AG.

  • Patient consent Obtained.

  • Ethics approval Derbyshire Research Ethics Committee (ref 09/H0401/44).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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