title: Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens.
abstract: The four major autoantigens (IA-2, IA-2 beta, GAD65 and insulin) of type 1 diabetes are all associated with dense core or synaptic vesicles. This raised the possibility that other secretory vesicle-associated proteins might be targets of the autoimmune response in type 1 diabetes. To test this hypothesis 56 proteins, two-thirds of which are associated with secretory vesicles, were prepared by in vitro transcription/translation and screened for autoantibodies by liquid phase radioimmunoprecipitation. Two secretory vesicle-associated proteins, VAMP2 and NPY, were identified as new minor autoantigens with 21% and 9%, respectively, of 200 type 1 diabetes sera reacting positively. These findings add support to the hypothesis that secretory vesicle-associated proteins are particularly important, but not the exclusive, targets of the autoimmune response in type 1 diabetes. Selective screening of the human proteome offers a useful approach for identifying new autoantigens in autoimmune diseases.
authors: Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. hhirai@mail.nih.gov
authors: Hiroki
authors: H
authors: Hirai
authors: Junnosuke
authors: J
authors: Miura
authors: Yafang
authors: Y
authors: Hu
authors: Helena
authors: H
authors: Larsson
authors: Karin
authors: K
authors: Larsson
authors: Ake
authors: A
authors: Lernmark
authors: Sten-A
authors: SA
authors: Ivarsson
authors: Tianxia
authors: T
authors: Wu
authors: Albert
authors: A
authors: Kingman
authors: Athanasios G
authors: AG
authors: Tzioufas
authors: Abner L
authors: AL
authors: Notkins
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000097:blood / Q000276:immunology*; D022142:Secretory Vesicles / Q000276:immunology*; D050988:Vesicle-Associated Membrane Protein 2 / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D009478:Neuropeptide Y; D050988:Vesicle-Associated Membrane Protein 2