Characterization of CD4+ T cells specific for glutamic acid decarboxylase (GAD65) and proinsulin in a patient with stiff-person syndrome but without type 1 diabetes

Diabetes Metab Res Rev. 2010 May;26(4):271-9. doi: 10.1002/dmrr.1083.

Abstract

Background: Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme in the synthesis of gamma-amino butyric acid (GABA) and an important autoantigen both in patients with type 1 diabetes (T1D) and stiff-person syndrome (SPS). Autoantibodies (GADA) to the 65-kDa isoform of GAD are a characteristic feature in both diseases. Approximately 30% of patients with SPS develop diabetes, yet, it is unclear to which extent co-existing autoimmunity to GAD65 and other islet autoantigens determines the risk of developing T1D.

Methods: In this study, we monitored CD4+ T-cell responses to GAD65 and proinsulin in a patient with SPS who remained normoglycaemic during the 46-month follow-up.

Results: Fluctuating but persistent T-cell reactivity to GAD65 was identified, as well as T-cell reactivity to proinsulin at one time point. The majority of the T-cell clones isolated from the patient with SPS produced high levels of Th2 cytokines (IL-13, IL-5 and IL-4). We also examined levels of GADA, insulin and IA-2 autoantibodies, and epitope specificity of GADA. In both serum and cerebrospinal fluid (CSF), GADA levels were high, and GADA persisted throughout the follow-up. Despite T-cell reactivity to both GAD65 and proinsulin, autoantibodies to other islet autoantigens did not develop.

Conclusions: Further follow-up will determine whether the beta-cell autoimmunity observed in this patient will eventually lead to T1D.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • CD4-Positive T-Lymphocytes / immunology*
  • Diabetes Mellitus, Type 1 / complications
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Proinsulin / immunology*
  • Stiff-Person Syndrome / complications
  • Stiff-Person Syndrome / immunology*

Substances

  • Autoantibodies
  • Proinsulin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2