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

SUMMARY 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‐γ 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.