Epitope Analysis Of Glutamic Acid Decarboxylase Autoantibody In Autoimmune Diabetes

Objective:Recent studies have shown that autoantibodies against the65-kDa isoform of glutamic acid decarboxylase (GAD65Ab) epitopes specific for autoimmune diabetes. However, little is known about the longitudinal changes in GAD65Ab epitopes recognition in autoimmune diabetes, and in Chinese population in particular. Therefore we explore the distribution and changes characteristics of GAD65Ab epitopes as well as the relationship between epitopes and islet β cell function in Chinese patients with type1diabetes(T1DM) and latent autoimmune diabetes in adults (LADA).Subjects and Methods1. T1DM and LADA patients with GAD A positive in the Second Xiangya Hospital of Central South University were enrolled from2005to2010. Out of them, we randomly collected34complete-data T1DM patients and66LADA patients who were followed up for three years. Furthermore,40patients with type2diabetes (T2DM) were selected as the control.2. The GAD65Abs reactivities to N-terminal (GAD65-N), Middle (GAD65-M) and C-terminal (GAD65-C) regions of GAD65of serum samples in patients with T1DM and LADA were measured by radioligand assay (RLA).3. The baseline clinical data of different GAD65Ab epitopes group in T1DM and LADA were compared, and the changes in GAD65Ab epitopes as well as fasting C-peptide levels during the follow-up period were also detected.Results1. The most frequent GAD65Ab epitopes pattern in T1DM patients was reactivity to the C-terminal which was higher than that in LADA patients (75.8%vs.38.7%, P=0.000). But for patients with LADA, their epitopes pattern primarily located in the middle terminal or C-terminal region of GAD65(43.5%and38.7%). 2. Whether in T1DM or in LADA patients, the GADA titers with reactivities to both middle terminal and C-terminal region were higher than that of reactivities to any epitopes of GAD65only group and no reactivity to any of the epitopes (P<0.05).3. LADA patients who had reactivities to N-terminal region of GAD65had higher fasting C-peptide levels than that with reactivities to C-terminal region only group and both middle terminal and C-terminal region group (P=0.007and P=0.009).4. During the3years follow-up period, no change was seen in epitopes distribution proportion either in T1DM or in LADA patients (P>0.05).5. During the3years follow-up period, the fasting C-peptide levels in T1DM patients with reactivities to any epitope of GAD65had declined, but no difference was seen in annual declining rate(P>0.05). There had a tendency that LADA patients with reactivities to any epitope of GAD65had higher annual declining rate in fasting C-peptide levels than that with no reactivity to any of the epitopes group and T2DM patients, but no statistical difference was seen (P>0.05).Conclusion:1. There are differences on the epitopes patterns of GAD65Ab between T1DM and LADA patients. Autoimmune diabetes patients with reactivities to multi-epitope present higher GADA titers, and those whose reactivities to C-terminal region have worse islet function.2. Disease course has no influence on the distribution proportion of GAD65Ab epitopes in autoimmune diabetes.3. There has a faster decline tendency in islet P cell function in LADA patients with reactivities to epitopes of GAD65than that with no reactivity to any of epitope and T2DM patients.