Characterization of the humoral immune response to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and/or type 1 diabetes.
OBJECTIVE
A humoral autoimmune response to glutamic acid decarboxylase (GAD65) is common both in patients with type 1 diabetes and in those with the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, while overt type 1 diabetes is relatively rarely diagnosed in APECED patients. The aim of this study was to assess whether this difference in the incidence of type 1 diabetes is associated with variability in the humoral immune response to GAD65, one of the major autoantigens in type 1 diabetes.


METHODS
Epitope- and isotype-specific GAD65 autoantibodies were analysed in 20 patients with APECED and 20 patients with newly diagnosed type 1 diabetes alone by radiobinding assays.


RESULTS
GAD65 autoantibodies targeted the middle and carboxy-terminal regions of GAD65 and occasionally the amino-terminal region in the APECED patients and comprised mainly the IgG1 subclass and less frequently the IgG2 and IgG4 subclasses. The profile of epitope- and isotype-specific GAD65 autoantibodies was similar in type 1 diabetes and APECED, except that IgG2 subclass antibodies were observed more often and at higher levels in the patients with type 1 diabetes alone (P < 0.05). None of the measured parameters separated APECED patients with type 1 diabetes from those without type 1 diabetes.


CONCLUSIONS
APECED-associated humoral autoimmunity to GAD65 does not differ markedly from that observed in type 1 diabetes; only IgG2-GAD65 antibodies may be more closely associated with the latter entity.
Ronkainen
Matti S
MS
Department of Pediatrics, University of Oulu, PO Box 5000, FI-90014 University of Oulu, Oulu, Finland.
Härkönen
Taina
T
Perheentupa
Jaakko
J
Knip
Mikael
M
D000328:Adult; D000917:Antibody Formation; D001323:Autoantibodies / Q000032:analysis*; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2