Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens.
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.
Hirai
Hiroki
H
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
Miura
Junnosuke
J
Hu
Yafang
Y
Larsson
Helena
H
Larsson
Karin
K
Lernmark
Ake
A
Ivarsson
Sten-A
SA
Wu
Tianxia
T
Kingman
Albert
A
Tzioufas
Athanasios G
AG
Notkins
Abner L
AL
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*
D001323:Autoantibodies; D001324:Autoantigens; D009478:Neuropeptide Y; D050988:Vesicle-Associated Membrane Protein 2