Hallford Philomena, Clair David St, Halley Lorna, Mustard Colette, Wei Jun
Division of Health Research, University of the Highlands and Islands, Centre for Health Science, Old Perth Road, Inverness IV2 3JH, UK.
Department of Medicine and Dentistry, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Schizophr Res. 2016 Oct;176(2-3):186-190. doi: 10.1016/j.schres.2016.07.020. Epub 2016 Jul 26.
Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.
流行病学研究揭示了1型糖尿病（T1D）与精神分裂症之间存在关联，但迄今为止报道的研究结果存在争议。为了澄清各研究之间的不一致性，对从272例精神分裂症患者和276例对照受试者采集的血浆样本中的T1D相关自身抗体进行了检测。使用三种线性肽抗原开发了一种内部酶联免疫吸附测定（ELISA），其中一种抗原来源于谷氨酸脱羧酶（GAD），另外两种来源于胰岛瘤相关抗原2（IA2）。曼-惠特尼U检验显示，与对照受试者相比，精神分裂症患者血浆中针对IA2b抗原的IgG水平显著降低（Z = -3.54，p = 0.0007），而在抗IA2a IgG水平（Z = -1.62，p = 0.105）或抗GAD IgG水平（Z = -1.63，p = 0.104）方面，这两组之间均未发现显著差异。线性回归分析表明，抗精神病药物与血浆中针对IA2a、IA2b或GAD的IgG水平无关，而这3种肽抗原的血浆IgG水平彼此显著相关。二元逻辑回归显示，无论是DQ2.5变体还是DQ8变体，在患者组和对照组中均与3种T1D相关自身抗体的循环水平无关。抗IA2a IgG测定的变异系数为10.7%，抗IA2b IgG测定为10.1%，抗GAD IgG测定为10.7%。目前的研究表明，T1D相关抗体不太可能导致精神分裂症风险，并且用线性肽抗原开发的内部ELISA具有高度可重复性。
