학술논문
Masked and Overt Autoantibodies Specific to the DPD Epitope of 65-kDa Glutamate Decarboxylase (GAD65-DPD) Are Associated With Preserved β-Cell Functional Reserve in Ketosis-Prone Diabetes
Document Type
Academic Journal
Author
Source
The Journal of Clinical Endocrinology & Metabolism. Jun 01, 2014 99(6):E1040-E1044
Subject
Language
English
ISSN
0021-972X
Abstract
CONTEXT:: Ketosis-prone diabetes (KPD), defined by presentation with diabetic ketoacidosis (DKA), comprises 4 subgroups based on the presence or absence of islet cell autoantibodies (A or A) and β-cell functional reserve (β or β). Among A KPD, autoantibody epitope reactivity to 65-kDa glutamate decarboxylase (GAD65), defined by monoclonal GAD65Ab(DPD), was associated with greater β-cell functional reserve. In a majority of healthy individuals, GAD65Ab are present in the sera but are masked by anti-idiotypic antibodies; in contrast, overtly GAD65Ab-positive patients with autoimmune type 1 diabetes patients lack these anti-idiotypic antibodies. OBJECTIVE:: Our objective was to determine the presence of masked and overt GAD65Ab(DPD) in relation to β-cell function and genetic risk factors in KPD patients. DESIGN:: We investigated the associations of masked and overt GAD65Ab(DPD) with β-cell functional reserve, and their relationship with human leukocyte antigen (HLA) class II haplotypes linked to autoimmune diabetes susceptibility or resistance, in a large KPD cohort. PATIENTS:: Adult KPD patients (n = 384) were followed longitudinally in a research clinic. MAIN OUTCOME MEASURES:: β-Cell function, autoantibody status, GAD65Ab epitopes, and HLA class II haplotypes were evaluated. RESULTS:: Overall, KPD patients with β-cell functional reserve (β subgroups) showed significantly higher frequency of masked GAD65Ab(DPD) than patients without β-cell functional reserve (β subgroups): 112 of 144 (79%) compared with 59 of 100 (59%), respectively (P = .002). Masked or overt GAD65Ab(DPD) were also more frequent among autoantibody-positive patients with preserved β-cell functional reserve (Aβ KPD) than those lacking β-cell function (Aβ KPD): 77% compared with 55% (P = .01). The susceptibility HLA haplotypes DQA1*0301/DQB1*0302 and DQA1*0301/DQB1*0201 were associated with absence of overt or masked GAD65Ab(DPD) (odds Ratios 2.3 and 2.2, respectively). CONCLUSIONS:: Masked GAD65Ab(DPD) are strongly associated with preserved β-cell functional reserve among patients with KPD. Absence of GAD65Ab(DPD) reactivity is associated with 2 HLA class II susceptibility haplotypes for autoimmune type 1 diabetes.