Neuropeptide Y is a minor autoantigen in newly diagnosed type 1 diabetes patients

作者：Skarstrand Hanna^*; Vaziri Sani Fariba; Delli Ahmed J; Torn Carina; Larsson Helena Elding; Ivarsson Sten; Agardh Daniel; Lernmark Ake

来源：Pediatric Diabetes, 2015, 16(8): 621-628.

DOI：10.1111/pedi.12222

• autoimmunity
• HLA genotype
• minor autoantibodies
• radioligand binding assay

BackgroundAutoantibodies (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.
MethodsSerum from the HLA-DQ typed T1D patients (n = 673; median age 10 yr) from Skane, 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.
ResultsA 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 ( = 0.63; p < 0.001) and the median levels correlated (R-2 = 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.
ConclusionsNPY is a minor autoantigen in children with newly diagnosed T1D. Therefore, NPY autoantibodies may be investigated in T1D autoimmunity.

• 出版日期2015-12