Serum glutamate decarboxylase antibodies and neurological disorders: when to suspect their association?

Neurol Sci. 2022 Jan;43(1):633-641. doi: 10.1007/s10072-021-05281-4. Epub 2021 Apr 29.

Abstract

Objectives: To explore different neurological manifestations with suspicion of being associated to serum glutamate decarboxylase antibodies (GAD-Abs) in order to better characterize anti-GAD neurological syndromes.

Methods: Observational retrospective study including all patients for whom GAD65-Abs titers in serum were requested by the Neurology Department at La Paz University Hospital between 2015 and 2019. GAD-Abs were measured by ELISA. Demographic data, neurological symptoms, comorbidity with diabetes mellitus (DM) or with another autoimmune disease, and GAD-Abs titers were studied. Stiff-person syndrome, ataxia, encephalitis, and epilepsy were considered typical anti-GAD neurological syndromes and were compared to other atypical manifestations.

Results: A total of 173 patients (51.7% men, mean age 51.62) were included. A progressive increase in requests of serum GAD-Abs has occurred over the last 5 years, especially in patients with atypical neurological manifestations. GAD-Abs were found in the serum of 22 patients (12.7%); of those, 15 (68.18%) suffered a typical anti-GAD syndrome. Presence of DM or another organ-specific autoimmune disease was predictive of GAD-AB seropositivity (p < 0.001). 6.6% of requested patients with an atypical syndrome had GAD-Abs, but serum levels were significantly lower than those found in patients with a typical syndrome (706.67 vs 1430.23 UI/mL; Mann-Whitney U, p = 0.034), and were finally diagnosed with another neurological disease.

Conclusion: Serum GAD-Abs were infrequently found in patients with clinical phenotypes other than those classically described as anti-GAD disorders, and with very low titers. In typical anti-GAD syndromes, there is a high comorbidity with DM and with other autoimmune diseases, and high serum GAD-Abs levels are usually present.

Keywords: Autoantibodies (GAD); Glutamate decarboxylase; Neurological autoimmune disorders.

Publication types

  • Observational Study

MeSH terms

  • Ataxia
  • Autoantibodies / blood*
  • Autoimmune Diseases
  • Comorbidity
  • Diabetes Mellitus
  • Encephalitis
  • Epilepsy
  • Female
  • Glutamate Decarboxylase / immunology
  • Humans
  • Male
  • Middle Aged
  • Nervous System Diseases* / diagnosis
  • Nervous System Diseases* / epidemiology
  • Retrospective Studies
  • Stiff-Person Syndrome

Substances

  • Autoantibodies
  • Glutamate Decarboxylase