Tobias Lohmann1, Jochen Sessler1, Hans-Joachim Verlohren2, Sabine Schröder3, Julia Rötger1, Karsten Dãhn1, Nils G. Morgenthaler1, Werner A. Scherbaum1
1Department of Internal Medicine III, Leipzig, Germany
2University of Leipzig Diabetes Specialty Practice, Leipzig, Germany
3Institute of Clinical Immunology and Transfusion Medicine Leipzig, Germany
Tóm tắt
OBJECTIVE
Young age at onset is a relevant parameter associated with a rapid progression of IDDM. Our major aim was to define differences between IDDM patients with age at diagnosis > 40 years and adult IDDM with onset at a younger age.
RESEARCH DESIGN AND METHODS
The correlation between islet-related antibodies (islet cell antibodies [ICAs] and antibodies [Abs] to GAD and the tyrosine phosphatase IA2), T-cell responses to GAD peptides and HLA class II isotypes was investigated in 23 IDDM patients 12–38 years of age at onset (group 1), 24 patients with IDDM > 40 years of age at onset (group 2), and 12 healthy control subjects. ICAs were measured by indirect immunofluorescence, and GAD-Ab and IA2-Ab were measured by immunoprecipitation tests. T-cell responses against GAD peptides, which had been identified as typical for IDDM, were tested by 5-day proliferation assays. HLA class II alleles were typed by polymerase chain reaction.
RESULTS
ICAs and GAD-Abs were more prevalent in IDDM patients than in control subjects (P < 0.001), but only IDDM group 1 had IA2-Abs (P < 0.001 compared with IDDM group 2 and control subjects). Moreover, antibody combinations differed between IDDM patients of groups 1 and 2. T-cell responses to GAD peptides were seen in 67% of IDDM group 1 and in 71% of IDDM group 2 (P < 0.02 compared with control subjects). IDDM patients of group 1 were more frequently DR4+/DQ8+ and less frequently DR2+/DQ0602+ compared with IDDM patients of group 2 (P < 0.05).
CONCLUSIONS
Our data provide strong evidence for humoral and cellular autoimmunity in adult IDDM patients with onset both before and after 40 years of age. However, late-onset differs from young-onset IDDM with respect to Ab profiles, especially a lack of IA2-Ab, and HLA class II types. These findings have consequences for the diagnostic strategy for identifying slow-onset IDDM in individuals after 40 years of age.
