Kawasaki Eiji, Tamai Hidekazu, Fukuyama Takahiro, Sagara Yoko, Hidaka Ryutaro, Uchida Aira, Tojikubo Masayuki, Tatsumoto Narihito, Akehi Yuko, Hiromatsu Yuji
The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan.
World J Diabetes. 2024 May 15;15(5):935-944. doi: 10.4239/wjd.v15.i5.935.
In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice.
To investigate the frequency of anti-islet autoantibodies in AITD patients.
Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D ( = 18), AITD with phenotypic type 2 diabetes (T2D) ( = 81), and AITD without diabetes ( = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups.
The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% 5.0%, < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups.
Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.
近年来，能够同时检测多种抗胰岛自身抗体的多重技术的出现，对于免疫介导的1型糖尿病（T1D）的分期和早期诊断具有特别重要的价值。虽然已经确定20%-30%的T1D患者患有自身免疫性甲状腺疾病（AITD），但关于AITD患者中抗胰岛自身抗体存在情况的可用数据有限。在市售的抗胰岛自身抗体中，谷氨酸脱羧酶65自身抗体（GADA）通常是一般临床实践中首先检测的标志物。
研究AITD患者中抗胰岛自身抗体的频率。
我们的研究纳入了495例AITD患者，分为三个不同的组：合并T1D的AITD（=18）、合并表型2型糖尿病（T2D）的AITD（=81）和无糖尿病的AITD（=396），并采用酶联免疫吸附测定（ELISA）来确定这些组中3种筛查胰岛细胞自身抗体（3种筛查ICA）、GADA、胰岛素瘤相关抗原2自身抗体（IA-2A）和锌转运体8自身抗体（ZnT8A）的频率。
合并T1D的AITD患者、合并T2D的AITD患者和无糖尿病的AITD患者中3种筛查ICA的频率分别为88.9%、6.2%和5.1%，后两组之间无显著差异。值得注意的是，与GADA相比，合并T1D的AITD患者中3种筛查ICA的频率高11.1%，合并T2D的AITD患者中高1.3%，无糖尿病的AITD患者中高1.1%。此外，3种筛查ICA阳性患者中分别有12.5%、20.0%和20.0%的GADA为阴性。另外，在合并T2D的AITD组和非糖尿病AITD组中，3种筛查ICA检测均为阴性患者中有1.3%的个体单个自身抗体检测为阳性。在3种筛查ICA阳性患者中，合并T1D的AITD患者中具有多种自身抗体的个体比例显著高于无糖尿病的患者（37.5%对5.0%，P<0.05）。然而，这一比例与合并T2D的AITD患者（20.0%）相似。不过，合并T1D的AITD患者和无糖尿病的AITD患者之间3种筛查ICA滴度无显著差异（436.8±66.4对308.1±66.4指数）。此外，在任何组中，格雷夫斯病和桥本甲状腺炎之间3种筛查ICA滴度均无显著差异。
我们的研究结果表明，一些无糖尿病的AITD患者的3种筛查ICA滴度与合并T1D的AITD患者相当。因此，在识别AITD患者中潜在的抗胰岛自身抗体阳性个体方面，3种筛查ICA优于GADA。
