Serum Levels Of Specific Autoantibodies In Patients With Autoimmune Diabetes And Thyroid Disease And Gene Polymorphism Correlation Analysis

Background: Type 1 diabetes(T1D) is an organ-specific autoimmune endocrine disease mediated by autoreactive T lymphocytes. The absolute lack of insulin in T1 D patients is caused by islet beta cells selective destruction. T1 D patients often tend to develop other autoimmune diseases, such as autoimmune thyroid disease(AITD) and coeliac disease(CD). T1 D, AITD and CD are all important parts of autoimmune polyglandular syndrome(APS). Specific autoantibodies can be detected in the serum of these patients.Objective: The aim of this study is to investigate the serum levels of GADA, IA-2A, Zn T8 A and tTGA in the patients with T1 D, AITD and APS3 v by radioligand assay. And analyze SLC30A8 gene polymorphism in patients with T1 D and type 2 diabetes(T2D).Methods: 272 patients with T1D(male 136 and female 136, aged 3 to 79 years old) were recruited from outpatient and inpatient department of the Second Hospital of Jilin University from December 2013 to October 2015. A total of 294 T2 D patients which were diagnosed within 12 months(male 178 and female 116, aged 11 to 80 years old) were enrolled as T2 D group. 188 patients with newly diagnosed AITD(male 33 and female 155, aged 5 to 79 years old) and 13 APS3 v patients with coexistence of T1 D and AITD(male 4 and female 9, aged 8 to 62 years old) were also selected in this study. 243 healthy volunteers with normal fasting and 2h postprandial blood glucose were recruited as control group. They have no autoimmune diseases and family history of autoimmune diseases. Informed consent was obtained from all patients and healthy controls. The serum levels of these specific autoantibodies were detected by radioligand assay and the SLC30A8 gene polymorphism was genotyped by PCR-direct sequencing. Data were analyzed by SPSS 21.0 statistic software.Results: The prevalence of GADA, IA-2A and Zn T8 A in T1 D patients was 45.4%(83/183), 31.7%(58/183) and 13.7%(25/183), respectively. The positive rates of these three islet autoantibodies were significantly higher than those in T2 D group and control group(p < 0.001). In AITD patients, the serum level of GADA was elevated compare to healthy controls(c2=11.587, p = 0.001). The positive rates of these three islet autoantibodies in APS3 v group were higher than AITD patients(p<0.05), and the prevalence of IA-2A and Zn T8 A were higher than T1 D patients(p<0.05). The serum tTGA positivity in patients with T1 D, AITD and APS3 v was higher than that in healthy controls(p<0.05). The SLC30A8 showed strong association to T2 D in genotype and allele frequency distribution(p<0.05) and the prevalence of C allele in Zn T8A-positive T1 D patients was significant higher than that in healthy controls(p < 0.05).Conclusions: The detection of multiple islet autoantibodies can increase the sensitivity of T1 D screening and GADA may help to diagnose AITD. Screening tTGA in T1 D or AITD patients can predict the development of CD. Further, screening multiple specific autoantibodies in T1 D or AITD patients has an important clinical value in early detection of APS3 v. The current study also confirmed the effects of SLC30A8 on risk for T2 D and the clear association between SLC30A8 gene polymorphism and Zn T8 A subtypes in Chinese T1 D patients.