Autoimmunity to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

Antibodies to glutamic acid decarboxylase (GAD) occur frequently in patient s with APECED, although clinical insulin-dependent diabetes mellitus (IDDM) is seen only in a subgroup of the patients. We studied the cellular immuni ty to GAD, antibodies to GAD and their association with the HLA DQB1 risk a lleles for IDDM in patients with APECED. Proliferation responses to GAD wer e enhanced in the patients with APECED when compared with the control subje cts (P = 0.004), but autoimmunity to GAD was not associated with IDDM in AP ECED. 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 patient s no difference in insulin secretion was observed in intravenous glucose to lerance test (IVGTT) between the patients with and without T cell reactivit y to GAD. We conclude that cellular immunity to GAD detected as T cell prol iferation 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 pa tients with clinically detectable beta-cell damage.