Maruyama Taro, Oak Shilpa, Shimada Akira, Hampe Christiane S
Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama, Japan.
Diabetes Care. 2008 Aug;31(8):1602-7. doi: 10.2337/dc08-0235. Epub 2008 May 16.
To determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes-like autoimmune response.
We correlated beta-cell-specific autoimmunity reflected in autoantibodies to the 65-kDa isoform of GAD (GAD65) with insulin requirement. We determined GAD65Ab epitope specificities in type 1 diabetic patients, LADA patients without insulin requirement (nonprogressed), and LADA patients that had developed insulin requirement (progressed).
Recognition of a type 1 diabetes-specific GAD65Ab epitope was more pronounced in type 1 diabetic patients than in nonprogressed (P < 0.001) or progressed (P < 0.01) LADA patients, with no significant differences between the two LADA cohorts. These differences were particularly pronounced in samples with GAD65Ab titers <1,000 units/ml, with no differences in epitope specificities in samples with higher GAD65Ab titers. Disease duration (initial diabetes diagnosis until sample collection or development of insulin requirement) in nonprogressed and progressed LADA patients, respectively, was not correlated with epitope specificity, suggesting lack of epitope maturation. This was supported by epitope analyses of longitudinal samples from LADA patients during progression to insulin requirement.
First, the GAD65Ab-specific autoimmune reaction in type 1 diabetic patients with low and moderate GAD65Ab titers differs from that in LADA patients, irrespective of insulin requirement. Second, the GAD65Ab-specific autoimmune response in LADA patients does not change after their initial diabetes diagnosis. Finally, LADA patients with high GAD65Ab titers resemble type 1 diabetic patients in their GAD65Ab epitope specificity.
确定成人隐匿性自身免疫性糖尿病（LADA）患者胰岛素需求的发展是否伴随着1型糖尿病样自身免疫反应的出现。
我们将针对65 kDa GAD同工型（GAD65）的自身抗体所反映的β细胞特异性自身免疫与胰岛素需求进行关联分析。我们测定了1型糖尿病患者、无胰岛素需求的LADA患者（未进展）以及已出现胰岛素需求的LADA患者（进展）中GAD65Ab表位特异性。
1型糖尿病患者中对1型糖尿病特异性GAD65Ab表位的识别比未进展的LADA患者（P < 0.001）或进展的LADA患者（P < 0.01）更为明显，两个LADA队列之间无显著差异。这些差异在GAD65Ab滴度<1000单位/ml的样本中尤为明显，而在GAD65Ab滴度较高的样本中表位特异性无差异。未进展和进展的LADA患者的病程（从最初糖尿病诊断到样本采集或出现胰岛素需求）分别与表位特异性无关，提示缺乏表位成熟。这在LADA患者进展至胰岛素需求过程中的纵向样本的表位分析中得到了支持。
第一，无论胰岛素需求如何，低和中度GAD65Ab滴度的1型糖尿病患者中GAD65Ab特异性自身免疫反应与LADA患者不同。第二，LADA患者在最初糖尿病诊断后其GAD65Ab特异性自身免疫反应未改变。最后，高GAD65Ab滴度的LADA患者在GAD65Ab表位特异性方面类似于1型糖尿病患者。
