TY - JOUR
T1 - GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study
AU - Hampe, Christiane S.
AU - Shojaie, Ali
AU - Brooks-Worrell, Barbara
AU - Dibay, Sepideh
AU - Utzschneider, Kristina
AU - Kahn, Steven E.
AU - Larkin, Mary E.
AU - Johnson, Mary L.
AU - Younes, Naji
AU - Rasouli, Neda
AU - Desouza, Cyrus
AU - Cohen, Robert M.
AU - Park, Jean Y.
AU - Florez, Hermes J.
AU - Valencia, Willy Marcos
AU - Stempel, Robert
AU - Palmer, Jerry P.
AU - Balasubramanyam, Ashok
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - 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 GAD65Abspecific 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.
AB - 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 GAD65Abspecific 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.
KW - T cell–mediated autoimmunity
KW - anti-idiotypic antibodies
KW - epitope-specific autoantibodies
KW - humoral autoimmunity
KW - islet autoantibodies
KW - latent autoimmune diabetes of adults
UR - http://www.scopus.com/inward/record.url?scp=85184742702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85184742702&partnerID=8YFLogxK
U2 - 10.1210/jendso/bvad179
DO - 10.1210/jendso/bvad179
M3 - Article
C2 - 38333889
AN - SCOPUS:85184742702
SN - 2472-1972
VL - 8
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
IS - 3
M1 - bvad179
ER -