T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity

Clin Exp Immunol. 2002 Sep;129(3):471-8. doi: 10.1046/j.1365-2249.2002.01931.x.

Abstract

Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-gamma after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / blood
  • Cells, Cultured
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / enzymology
  • Cerebellar Ataxia / immunology*
  • Child
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Glutamate Decarboxylase / immunology*
  • Histocompatibility Testing
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Polyendocrinopathies, Autoimmune / diagnosis
  • Polyendocrinopathies, Autoimmune / enzymology
  • Polyendocrinopathies, Autoimmune / immunology*
  • Stiff-Person Syndrome / diagnosis
  • Stiff-Person Syndrome / enzymology
  • Stiff-Person Syndrome / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Autoantibodies
  • Cytokines
  • Glutamate Decarboxylase