Abstract
Context
Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels.
Context
In this study, we aimed to better characterize islet autoantibodies in this T2D cohort. This is an ancillary study to NCT01794143.
Methods
We stringently defined GAD65Ab positivity with a competition assay, analyzed GAD65Ab-specific epitopes, and measured GAD65Ab-specific anti-Id in serum.
Results
Competition assays confirmed that 5.9% of the patients were GAD65Ab positive, but beta-cell function was not associated with GAD65Ab positivity, GAD65Ab epitope specificity or GAD65Ab-specific anti-Id. GAD65-related autoantibody responses in GRADE T2D patients resemble profiles in healthy individuals (low GAD65Ab titers, presence of a single autoantibody, lack of a distinct epitope pattern, and presence of anti-Id to diabetes-associated GAD65Ab). In this T2D cohort, GAD65Ab positivity is likely unrelated to the pathogenesis of beta-cell dysfunction.
Conclusion
Evidence for islet autoimmunity in the pathophysiology of T2D beta-cell dysfunction is growing, but T1D-associated autoantibodies may not accurately reflect the nature of their autoimmune process.
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Details
1 Immusoft , Seattle, WA 98103 , USA
2 Department of Biostatistics, Department of Medicine, University of Washington , Seattle, WA 98185 , USA
3 Massachusetts General Hospital Diabetes Center , Harvard Medical School, Boston, MA 02114 , USA
4 International Diabetes Center , Minneapolis, MN 55416 , USA
5 The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University , Rockville, MD 20852 , USA
6 Department of Medicine, University of Colorado School of Medicine , Aurora, CO 80045 , USA
7 Division of Diabetes, Endocrinology and Metabolism, University of Nebraska and Omaha VA Medical Center , Omaha, NE 68198 , USA
8 Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati and Cincinnati VA Medical Center , Cincinnati, OH 45221 , USA
9 Medstar Health, Hyattsville , MD 20782 , USA
10 Department of Medicine, University of Miami , Miami, FL 33135 , USA
11 Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina , Charleston, SC 29425 , USA
12 Department of Public Health, College of Health and Urban Affairs, Florida International University , Miami, FL 33181 , USA
13 Department of Medicine: Endocrinology, Diabetes and Metabolism, Baylor College of Medicine , Houston, TX 77030 , USA