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

Authors: Klemetti, P.; Björses, P.¹; Tuomi, T.²; Perheentupa, J.³; Partanen, J.⁴; Rautonen, N.⁵; Hinkkanen, A.⁶; Ilonen, J.⁶; Vaarala, O.⁷

Source: Clinical & Experimental Immunology, Volume 119, Number 3, March 2000 , pp. 419-425(7)

Publisher: Blackwell Publishing

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Abstract:

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-γ) 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-γ secretion by GAD-stimulated T cells was frequent in patients with APECED (69%) and was not restricted to the patients with clinically detectable β-cell damage.

Keywords: GAD antibodies; insulin-dependent diabetes; HLA; cytokines; T lymphocytes

Document Type: Research article

DOI: 10.1046/j.1365-2249.2000.01167.x

Affiliations: 1: Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland, 2: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, 3: Hospital for Children and Adolescents, University of Helsinki, and 4: Tissue Typing Laboratory, Finnish Red Cross Blood Transfusion Service and 5: Danisco Cultor, Kirkhönummi, Finland, and 6: Turku Immunology Centre and the Department of Virology, University of Turku, Turku, Finland 7: Department of Biochemistry, National Public Health Institute,

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