Abstract
Previous scientific data suggest that beta-cell destruction
in type 1 diabetes is mediated by an autoimmune process. This work
was aimed at expanding existing knowledge of humoral autoimmunity
by analysing antibodies against the intracellular part of the IA-2
protein (IA-2A) in 1200 patients with the disease, 750 siblings
and more than 370 non-diabetic controls.
IA-2A were present at the time of diagnosis in the overwhelming
majority of patients with type 1 diabetes, and were associated with
human leucocyte antigen (HLA) DR4 and DQB1*0302, but not with
gender. Humoral autoimmunity was more marked in patients diagnosed
when younger than 20 years of age than in older ones, but no noticeable
association was observed between IA-2A and age under the age of
20 years. IA-2A in combination with antibodies to GAD65 (GADA) identified
a higher proportion of patients younger than 15 years of age at
the time of diagnosis than did islet cell antibodies (ICA) alone.
The levels of IA-2A and the proportions of antibody-positive
patients decreased with increasing duration of type 1 diabetes,
although more than half of the patients still tested positive for
IA-2A after 10 years of clinical disease.
IA-2A, GADA, insulin autoantibodies (IAA) and ICA were detected
with individual fluctuations in 8-14% of the siblings of
children with type 1 diabetes monitored from the time of diagnosis
of the proband, and the fluctuations were modified by HLA-defined
genetic susceptibility, age of the siblings, family size and total
number of detectable autoantibodies. IA-2A positivity detected at
the time of diagnosis of the proband increased the risk of future
disease in the siblings. The positive predictive value increased
with increasing IA-2A levels, although individual risk assessment appeared
to be a complex matter.
In conclusion, IA-2 appears to be an important autoantigen
in type 1 diabetes, since IA-2A is associated with the HLA haplotype
that most strongly predisposes subjects to the disease and have the
highest positive predictive value for future disease out of the
four autoantibodies used for risk assessment purposes.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5677-8 |
| Date | 29 May 2000 |
| Creators | Savola, K. (Kaisa) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2000 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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