Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

NPY minor autoantibodies in newly diagnosed type 1 diabetes patients. (#120)

Hanna Skärstrand 1 , Fariba Vaziri-Sani 1 , Cecilia Andersson 1 , Helena Elding Larsson 1 , Sten Ivarsson 1 , Åke Lernmark 1 , Skåne Study Group
  1. Clinical Sciences, Lund University, Skåne University Hospital SUS, Malmö, Skåne, Sweden

Background: Autoantibodies against the neurotransmitter, Neuropeptide Y (NPY), was reported in 9% of newly diagnosed type 1 diabetes (T1D) patients. A SNP at rs16139 (T1128C) within the NPY-gene identified an aa substitution from Leucine (L) to Proline (P) (L7P) associated with impaired glucose tolerance and an increased risk for Type 2 diabetes. We aim to determine 1) the influence of NPY-LA and NPY-PA on the diagnostic sensitivity of T1D, 2) the association of the NPYA variants with the major islet autoantibodies, and 3) the association of NPYA to HLA-DQ genotypes in newly diagnosed T1D patients.

Materials and methods: Newly diagnosed T1D patients (n=675; median age 10.2 years) from Skåne, Sweden, were recruited between 1996 and 2005. Serum samples at diagnosis were analyzed for autoantibodies against NPY-L and NPY-P in a Radiobinding assay and against insulin, GAD65, IA-2, ZnT8. Patients were HLA-DQ genotyped. Control samples were obtained from 398 healthy blood donors in Skåne 2004.

Results: The frequency of positive T1D patients was 17% (n=115) for NPY-LA (p<0.001) and 24% (n=161) for NPY-PA (p<0.001) as compared to 1% (n=4) of controls. By including the NPY-LA and NPY-PA to the major autoantibodies the autoantibody negative T1D patients were reduced from 5.5% (n=37) to 4.8% (n=32). Median levels of NPY-LA were higher in both T1D patients (31 U/mL; p<0.001) and controls (23 U/mL; p<0.001) compared to the levels of NPY-PA in T1D patients (26 U/mL; p<0.001) and controls (16 U/mL; p<0.001). The levels of the two NPYA variants were strongly correlated (R2=0.631; p<0.001). Neither of the NPYA variants appeared with any of the GADA, IAA, IA-2A nor the ZnT8A. There were no associations between the NPYA positive patients and the HLA-DQ genotypes.

Conclusion: NPY is a minor autoantigen in newly diagnosed T1D patients and therefore, autoantibodies against NPY should be investigated in the autoimmunity of T1D.