ss-cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the autoimmune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. Autoantibodies against the IA-2 tyrosine phosphatase-like protein (IA-2 ab) or insulin (IAA) have been suggested to be better markers for active ss-cell destruction. We studied these antibodies in sera from 60 Finnish patients with APECED, 12 of whom subsequently developed type 1 diabetes. Four (36%) of the 11 patients for whom we had prediabetic samples had IA-2 ab, and 4 (36%) had IAA. None of the 48 nondiabetics had IAA, and only 2 (4%) had IA-2 ab. Both had the antibodies for years without diabetes. Thus, IA-2 ab or IAA have a low sensitivity (36%), but high specificity (96% or 100%), with a positive predictive value of 67% for type 1 diabetes in patients with APECED. Data for human leukocyte antigen haplotypes were available for 59 of the patients, including 11 diabetics, and for 8 additional nondiabetic Finnish patients. No association between type 1 diabetes and high risk genotypes was seen. None of the 11 patients with type 1 diabetes, but 15 of the 56 (27%; P: < 0.05) nondiabetic patients and 24 of 93 (26%; P: < 0.05) of the control subjects had the DQB1*0602 allele, which is considered protective for type 1 diabetes. This is remarkable, as previously no positive or negative associations have been reported for any disease components of APECED with human leukocyte II antigens.
Gylling
M
M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Tuomi
T
T
Björses
P
P
Kontiainen
S
S
Partanen
J
J
Christie
M R
MR
Knip
M
M
Perheentupa
J
J
Miettinen
A
A
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies; D007328:Insulin; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2