Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults

Gleichmann, Helga; Zörcher, B.; Greulich, B.; Gries, F. A.; Henrichs, H. R.; Bertrams, J.; Kolb, Hubert

doi:10.1007/bf00275656

Cited by 81 publications

(27 citation statements)

References 10 publications

(12 reference statements)

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“…14,16 Patients with late-onset diabetes who show ICA titers are more likely to carry HLA-DR3 and/or DR4 and to exhibit progressive beta cell damage, and thus subjected to insulin treatment. 17 In contrast to findings in some Caucasian groups of diabetics whose disease is associated with other organspecific autoantibodies, 14,18 none of our patients who were ICA positive had other autoantibodies. This corroborates findings from studies conducted on Nigerian and Pima Indian diabetics.…”

Section: Discussioncontrasting

confidence: 88%

Frequency of Islet Cell Antibodies in Adult Newly Diagnosed Diabetic Patients

et al. 1990

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The sera of 138 Saudi patients with newly diagnosed diabetes (age, 24 to 75 years) were tested for islet-cell autoantibody (ICA), complement-fixing islet cell antibody (CF-ICA), and thyroid, stomach, and antinuclear autoantibodies. The autoantibody tests were also done on 70 nondiabetic normal control subjects matched for age, sex, and weight. Total ICA tests were positive in 13% (18/138) of the diabetics above age 35 years. Six of these sera also fixed complement. A significant incidence of ICA in each subgroup was noted in the following age ranges: 35-44 (12.8%), 45-54 (14.3%), and above 60 years (29.4%). Moreover, the incidence was higher in females (8.7% ; 12/138) than in males (4.3% ; 6/138). These differences were significant (P < 0.001). Control group subjects were all ICA negative. In relation to age at onset above 35 years, Saudi adult diabetics appeared to be characterized by the ICA marker, indicating ongoing beta cell damage and possible subsequent insulin dependency. Thyroid, gastric parietal cell, and antinuclear autoantibodies were absent in the ICA-positive patients but were present in 36.6% (44/120) of the diabetic ICA-negative subjects as well as in 45.7% (32/ 70) of the control subjects. This absence of other organ-specific antibodies in ICA-positive subjects could be due to an altered immunological state produced by

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Section: Discussioncontrasting

confidence: 88%

Frequency of Islet Cell Antibodies in Adult Newly Diagnosed Diabetic Patients

et al. 1990

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“…This latter form of diabetes had been described previously and the presence of ICA positivity shown [45,46]. The lack of accessibility for most clinicians to the ICA immuno-fluorescent assay even in developed countries, along with the technical difficulties, made it, however, totally unsuitable for widespread use for classification.…”

Section: Diabetes Classification ± a Non-stop Evolution And Revolutionmentioning

confidence: 67%

Diabetes epidemiology as a tool to trigger diabetes research and care

1999

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“…Type II diabetic patients with ICA can have a higher than expected prevalence of HLA DRB1 alleles usually associated with Type I diabetes [17,18]. Concentrating on the combinations of DRB1 and DQB1 that can represent high-risk haplotypes in white Caucasian populations we have examined whether adult-onset patients, who at diagnosis did not require insulin therapy and were thought to have Type II diabetes, have an increased prevalence of HLA DRB1 and DQB1 genotypes that predispose to autoimmune Type I diabetes.…”

mentioning

confidence: 99%

Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43)

Horton

Stratton

Bottazzo³

et al. 1999

Diabetologia

104

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Aims/hypothesis. Juvenile-onset, insulin-dependent diabetes is associated with islet cell antibodies and with specific ªhigh-riskº HLA-DRB1 and HLA-DQB1 genotypes. Patients with Type II (non-insulin-dependent) diabetes mellitus can have islet-related antibodies, but the genotypic associations at different ages of onset have not been evaluated. Our aim was to determine (i) the prevalence of DRB1 and DQB1 genotypes in patients at diagnosis of Type II diabetes at different ages from 25 to 65 years compared with the general population, and (ii) whether the presence of islet cell antibodies (ICA) or glutamic acid decarboxylase antibodies (GADA) or both by age is associated with different DRB1 and DQB1 genotypes. Methods. The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1*03 and DRB1*04 and the high-risk DRB1*04-DQB1* 0302 haplotype. To assess over-representation of high-risk alleles for Type I (insulin-dependent) diabetes mellitus, the prevalence of high-risk alleles in diabetic patients was expressed relative to the prevalence of low-risk alleles, non-DR3/non-DR4, that provided a reference denominator in both the diabetic patients and in 200 non-diabetic control subjects. The prevalence of ICA or GADA or both in patients with different HLA genotypes was assessed in those diagnosed in four age groups, 25±34 years, 35±44 years, 45±54 years and 55±65 years. Results. In Type II diabetic patients presenting at ages 25±34, 35±44 and 45±54 years, there was an increased prevalence of DR3/DR4 compared with the general population with approximately 6.5-fold, 2.9-fold, 2.1-fold over-representation, respectively (p < 0.0001, < 0.01, < 0.05) but this was not found in those aged 55±65 years old. In the group aged 25±34 years, 32 % of patients with ICA or GADA or both had DRB1*03/DRB1*04-DQB1*0302 compared with 10 % in those aged 55±65 years and expected 3 % prevalence. Conversely, only 14 % of those aged 25±34 years with antibodies had non-DR3/non-DR4, compared with 35 % in those aged 55±65 years. There was thus pronounced age heterogeneity in DRB1 and DQB1 predisposition to Type II diabetes. The antibodies displaced DRB1 or DQB1 genotypes in the multivariate model for requiring insulin therapy by 6 years of follow-up. Conclusion/hypothesis. The age of presentation of Type I diabetes in adulthood was in part dependent on the DRB1/DQB1 genotype. Islet cell antibodies and glutamic acid decarboxylase antibodies were strongly associated with DRB1*03/DRB1*04-DQB1*0302 in early adulthood but showed little relation with specific HLA genotypes after the age of 55 years. [Diabetologia (1999) 42: 608±616]

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Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults

Cited by 81 publications

References 10 publications

Frequency of Islet Cell Antibodies in Adult Newly Diagnosed Diabetic Patients

Frequency of Islet Cell Antibodies in Adult Newly Diagnosed Diabetic Patients

Diabetes epidemiology as a tool to trigger diabetes research and care

Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43)

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