ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies

Journal of Autoimmunity
Dongmei MiaoFrancesco Dotta

Abstract

ICA512/IA-2, a tyrosine phosphatase-like protein, is one of the major autoantigens in type 1 diabetes. Following phage display characterization of ICA512 autoantigenic epitopes, we developed fluid phase autoantibody radioimmunoassays for a series of ICA512 fragments (F1 [amino acids (aa): 761-964], F2A [aa 256-760], F2B [aa 761-928], and F2C [aa 929-979]). With the hypothesis that 'non-diabetes associated' ICA512 autoantibodies would differ from diabetes associated ICA512 autoantibodies in terms of epitopes recognized, we analyzed ten such serum samples (two from normal control individuals, one from a general population subject with transient ICA512 autoantibodies and seven from relatives of patients with type 1 diabetes who had single transient ICA512 positivity). All but one of the 'non-diabetes associated' ICA512 positive samples (9/10) did not react with Fragment 1 which contains the major antigenic epitopes of the molecule that were recognized by almost all (51/52) ICA512 positive new onset patient samples and pre-diabetic relatives (P< 10(-6)). The great majority of samples (44/52) from the new onset patients and pre-diabetic relatives reacted with at least two fragments and 60% (31/52) with three or more fragments. In co...Continue Reading

References

Nov 1, 1995·Diabetes·R GiananiG S Eisenbarth

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Citations

Jun 29, 2013·Diabetes Technology & Therapeutics·Marian Rewers
Oct 7, 2004·Journal of the Neurological Sciences·John J HongHarvey S Singer
Nov 25, 2005·Diabetes·Catherine PihokerAke Lernmark
Oct 4, 2020·Diabetes & Metabolism·Natalie YoussefAssaad A Eid
Apr 22, 2021·Endocrine Reviews·Michelle SoCarla J Greenbaum

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