β-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...
Gespeichert in:
Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2000-12, Vol.85 (12), p.4434-4440 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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 β-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. |
---|---|
ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.85.12.7120 |