TY - JOUR
T1 - Autoantibodies to the IA-2 extracellular domain refine the definition of “A+” subtypes of ketosis-prone diabetes
AU - Mulukutla, Surya N.
AU - Acevedo-Calado, Maria
AU - Hampe, Christiane S.
AU - Pietropaolo, Massimo
AU - Balasubramanyam, Ashok
N1 - Funding Information:
Funding. This work was supported by the Robert and Janice McNair Foundation, JDRF grant 17-2012-688 (to M.P.), and National Institute of Diabetes and Digestive and Kidney Diseases grants R01-DK-53456 (to M.P.) and R01-DK-1041411 (to A.B.). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. S.N.M. performed the calculations, collected the clinical data, and drafted the manuscript. M.A.-C. performed the IA2-EC and IA2-FL autoantibody analyses and calculations. C.S.H. performed the initial autoantibody analyses to phenotype the patients with KPD. M.P. and A.B. designed the research, interpreted the data, and had primary responsibility for the final content. All authors edited and approved the final manuscript. M.P. and A.B. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at ENDO 2017: The 99th Annual Meeting of The Endocrine Society, Orlando, FL, 1–4 April 2017.
Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - OBJECTIVE Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), >60% of adults lack three classic islet autoantibodiesdIA-2, GAD65, and ZnT8 Absdassociated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative (“A2”) KPD patients possess occult IA-2 Ab directed against full-length IA-2 (IA-2FL) or its extracellular domain (IA-2EC). RESEARCH DESIGN AND METHODS We developed an assay that targets IA-2FL and IA-2EC and used it to analyze 288 subjects with A2 KPD. RESULTS Ten A2 KPD patients were positive for IA-2EC Ab (3.5%), and three were also positive for IA-2FL Ab (1.0%), similar to frequencies in type 1 and type 2 diabetes. CONCLUSIONS Measurement of IA-2FL Ab and IA-2EC Ab improves the accuracy of the Ab classification of KPD patients.
AB - OBJECTIVE Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), >60% of adults lack three classic islet autoantibodiesdIA-2, GAD65, and ZnT8 Absdassociated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative (“A2”) KPD patients possess occult IA-2 Ab directed against full-length IA-2 (IA-2FL) or its extracellular domain (IA-2EC). RESEARCH DESIGN AND METHODS We developed an assay that targets IA-2FL and IA-2EC and used it to analyze 288 subjects with A2 KPD. RESULTS Ten A2 KPD patients were positive for IA-2EC Ab (3.5%), and three were also positive for IA-2FL Ab (1.0%), similar to frequencies in type 1 and type 2 diabetes. CONCLUSIONS Measurement of IA-2FL Ab and IA-2EC Ab improves the accuracy of the Ab classification of KPD patients.
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U2 - 10.2337/dc18-0613
DO - 10.2337/dc18-0613
M3 - Article
C2 - 30327357
AN - SCOPUS:85056802814
SN - 0149-5992
VL - 41
SP - 2637
EP - 2640
JO - Diabetes care
JF - Diabetes care
IS - 12
ER -