T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity.
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.
Immunology Unit, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Spain.
M
M
Costa
A
A
Saiz
R
R
Casamitjana
M Fernández
MF
Castañer
A
A
Sanmartí
F
F
Graus
D
D
Jaraquemada
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002478:Cells, Cultured; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology*; D016750:Stiff-Person Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D005968:Glutamate Decarboxylase