Work

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of “A+” Subtypes of Ketosis-Prone Diabetes

Year: 2018

Type: article

Abstract: 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 autoantibodies-IA-2, GAD65, and ZnT8 Abs-associated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative ("A-") 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 A- KPD. RESULTS: Ten A- 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 Aβ classification of KPD patients.

Source: Diabetes Care

DOI: 10.2337/dc18-0613

Authors: Surya N. Mulukutla, Maria Acevedo-Calado, Christiane S. Hampe, Massimo Pietropaolo, Ashok Balasubramanyam

Institutions: Baylor College of Medicine, University of Washington

Language: English

Topic: Diabetes and associated disorders

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Juvenile Diabetes Research Foundation United States of America, National Institute of Diabetes and Digestive and Kidney Diseases