Skärstrand Hanna, Vaziri-Sani Fariba, Delli Ahmed J, Törn Carina, Elding Larsson Helena, Ivarsson Sten, Agardh Daniel, Lernmark Åke
Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
Pediatr Diabetes. 2015 Dec;16(8):621-8. doi: 10.1111/pedi.12222. Epub 2014 Sep 25.
Autoantibodies (A) against Neuropeptide Y (NPY), was reported in 9% newly diagnosed type 1 diabetes (T1D) patients. A single nucleotide polymorphism (SNP) at rs16139 (T1128C) within the NPY-gene identified an amino acid substitution from leucine (L) to proline (P) (L7P) associated with both glucose tolerance and type 2 diabetes. We aimed to determine: (i) the influence of autoantibodies to leucine neuropeptide Y (NPY-LA) and autoantibodies to proline neuropeptide Y (NPY-PA) on the diagnostic sensitivity of type 1 diabetes (T1D), (ii) the association of NPYA with major islet autoantibodies, and (iii) the association of NPYA with HLA-DQ genotypes in newly diagnosed T1D patients.
Serum from the HLA-DQ typed T1D patients (n = 673; median age 10 yr) from Skåne, Sweden, were analyzed for autoantibodies against NPY-L and NPY-P in a radioligand binding assay, and against glutamic acid decarboxylase 65 (GAD65), insulin, insulinoma associated protein-2 (IA-2), and zinc transporter 8 (ZnT8) in addition to islet cell antibodies (ICA). A total of 1006 subjects (median age 9 yr) were used as controls.
A total of 9.2% (n = 62) of the T1D patients were positive for NPY-LA (p < 0.001) and 7.6% (n = 51) for NPY-PA (p < 0.001) compared to 1.1% (n = 11) in controls. The NPY-LA and NPY-PA appeared together (κ = 0.63; p < 0.001) and the median levels correlated (R² = 0.603; p < 0.001). T1D patients diagnosed after 10 yr of age were at an increased risk for NPYA at diagnosis [odds ratio (OR = 2.46; 95% CI 1.46-4.16; p = 0.001)] adjusted for age at diagnosis, gender, autoantibody positivity, and HLA.
NPY is a minor autoantigen in children with newly diagnosed T1D. Therefore, NPY autoantibodies may be investigated in T1D autoimmunity.
在9%新诊断的1型糖尿病（T1D）患者中报告了针对神经肽Y（NPY）的自身抗体（A）。NPY基因中rs16139（T1128C）处的单核苷酸多态性（SNP）确定了一个氨基酸替换，即从亮氨酸（L）替换为脯氨酸（P）（L7P），这与葡萄糖耐量和2型糖尿病相关。我们旨在确定：（i）抗亮氨酸神经肽Y自身抗体（NPY-LA）和抗脯氨酸神经肽Y自身抗体（NPY-PA）对1型糖尿病（T1D）诊断敏感性的影响，（ii）NPYA与主要胰岛自身抗体的关联，以及（iii）新诊断的T1D患者中NPYA与HLA-DQ基因型的关联。
对来自瑞典斯科讷的HLA-DQ分型的T1D患者（n = 673；中位年龄10岁）的血清进行放射性配体结合试验，分析其针对NPY-L和NPY-P的自身抗体，以及针对谷氨酸脱羧酶65（GAD65）、胰岛素、胰岛素瘤相关蛋白-2（IA-2）和锌转运体8（ZnT8）的自身抗体，此外还检测了胰岛细胞抗体（ICA）。总共1006名受试者（中位年龄9岁）用作对照。
与对照组的1.1%（n = 11）相比，T1D患者中共有9.2%（n = 62）的NPY-LA呈阳性（p < 0.001）以及7.6%（n = 51）的NPY-PA呈阳性（p < 0.001）。NPY-LA和NPY-PA同时出现（κ = 0.63；p < 0.001），且中位水平具有相关性（R² = 0.603；p < 0.001）。在根据诊断年龄、性别、自身抗体阳性情况和HLA进行调整后，10岁以后诊断的T1D患者在诊断时出现NPYA的风险增加[比值比（OR = 2.46；95%可信区间1.4(1/2)-4.16；p = 0.001）]。
NPY是新诊断的T1D儿童中的次要自身抗原。因此，可在T1D自身免疫中研究NPY自身抗体。
