title: Neuropeptide Y is a minor autoantigen in newly diagnosed type 1 diabetes patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  NPY is a minor autoantigen in children with newly diagnosed T1D. Therefore, NPY autoantibodies may be investigated in T1D autoimmunity.
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Skärstrand
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Fariba
authors.initials: F
authors.lastname: Vaziri-Sani
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Ahmed J
authors.initials: AJ
authors.lastname: Delli
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Elding Larsson
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Ivarsson
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Agardh
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Skåne University Hospital, SE-20502, Malmö, Sweden.
authors.forename: Åke
authors.initials: Å
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D001323:Autoantibodies; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009478:Neuropeptide Y / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D009478:Neuropeptide Y
keywords: HLA genotype; autoimmunity; minor autoantibodies; radioligand binding assay