title: Antiislet autoantibodies usually develop sequentially rather than simultaneously.
abstract: The goal of this study was to address whether antiislet autoantibodies appear sequentially or simultaneously before the onset of type I diabetes. We analyzed sequential serum samples from 155 siblings and offspring (aged < 7 yr) of patients with type I diabetes from the Denver Diabetes Autoimmunity Study in the Young study and from a separate group of first degree relatives (aged 2-40 yr) for autoantibodies reacting with three defined autoantigens: glutamic acid decarboxylase (GAD65), insulin, and ICA512/IA-2. The youngest age at which 1 of the 3 autoantibodies appeared was 1.1 yr, and the oldest was 60.9 yr. Of the total 26 autoantibody conversion events observed, in only 3 instances did more than 1 autoantibody appear simultaneously. Among individuals (n = 12) with sequential conversion to expression of multiple autoantibodies, anti-GAD65 autoantibodies or antiinsulin autoantibodies appeared first (4 expressed antiinsulin autoantibodies first, and 8 anti-GAD65 autoantibodies first). We conclude that antiislet autoantibodies usually appear sequentially and not simultaneously. This corroborates early suggestions that humoral autoimmunity to islets develops chronically in a process usually measured in months to years. As expression of multiple autoantibodies is associated with a high risk of progression to diabetes, and sequential appearance of autoantibodies can occur late in life, long term follow-up is necessary to fully delineate the relationship of diabetes risk to autoantibody expression.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver 80262, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Rewers
authors.forename: R
authors.initials: R
authors.lastname: Gianani
authors.forename: E
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Verge
authors.forename: P
authors.initials: P
authors.lastname: Chase
authors.forename: G
authors.initials: G
authors.lastname: Klingensmith
authors.forename: H
authors.initials: H
authors.lastname: Erlich
authors.forename: J
authors.initials: J
authors.lastname: Norris
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001323:Autoantibodies / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D008875:Middle Aged
chemical_list: D001323:Autoantibodies