Autoimmunity to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal...

Antibodies to glutamic acid decarboxylase (GAD) occur frequently in patients with APECED, although clinical insulin-dependent diabetes mellitus (IDDM) is seen only in a subgroup of the patients. We studied the cellular immunity to GAD, antibodies to GAD and their association with the HLA DQB1 risk alleles for IDDM in patients with APECED. Proliferation responses to GAD were enhanced in the patients with APECED when compared with the control subjects (P = 0.004), but autoimmunity to GAD was not associated with IDDM in APECED. The levels of interferon-gamma (IFN-gamma) secreted by GAD-stimulated T cells were higher in the patients than in control subjects (P = 0. 001). A negative correlation (r = - 0.436, P = 0.03) existed between the antibody levels and the stimulation indices (SIs) to GAD. In 14 non-diabetic patients no difference in insulin secretion was observed in intravenous glucose tolerance test (IVGTT) between the patients with and without T cell reactivity to GAD. We conclude that cellular immunity to GAD detected as T cell proliferation response to GAD or IFN-gamma secretion by GAD-stimulated T cells was frequent in patients with APECED (69%) and was not restricted to the patients with clinically detectable beta-cell damage.