Analysis of serum Hsp90 as a potential biomarker of β cell autoimmunity in type 1 diabetes

Gail J. Ocaña, Emily K. Sims, Renecia A. Watkins, Susanne Ragg, Kieren Mather, Richard A. Oram, Raghu Mirmira, Linda DiMeglio, Janice Blum, Carmella Evans-Molina

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Abstract

Heat shock protein 90 (Hsp90) is a protein chaperone that is upregulated and released from pancreatic β cells under pro-inflammatory conditions. We hypothesized that serum Hsp90 may have utility as a biomarker of type 1 diabetes risk and exhibit elevations before the onset of clinically significant hyperglycemia. To this end, total levels of the alpha cytoplasmic isoform of Hsp90 were assayed in autoantibody-positive progressors to type 1 diabetes using banked serum samples from the TrialNet Pathway to Prevention Cohort that had been collected 12 months prior to diabetes onset, with comparison to age, sex, and BMI-category matched autoantibody-positive nonprogressors and healthy controls. Hsp90 levels were higher in autoantibody-positive progressors and nonprogressors 18 years of age compared to matched healthy controls. However, Hsp90 levels were not different between progressors and nonprogressors in any age group. Hsp90 was positively correlated with age in control subjects, but this correlation was absent in autoantibody positive individuals. In aggregate these data indicate that elevated Hsp90 levels are present in youth with β cell autoimmunity, but are not able to distinguish youth or adult type 1 diabetes progressors from nonprogressors in samples collected 12 months prior to diabetes development.

Original languageEnglish (US)
Article numbere0208456
JournalPLoS One
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2019

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HSP90 Heat-Shock Proteins
autoimmunity
insulin-dependent diabetes mellitus
Biomarkers
Medical problems
Autoimmunity
Type 1 Diabetes Mellitus
blood proteins
Blood Proteins
biomarkers
autoantibodies
Autoantibodies
cells
diabetes
protein aggregates
hyperglycemia
heat-shock protein 90
Hyperglycemia
Protein Isoforms
Age Groups

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Analysis of serum Hsp90 as a potential biomarker of β cell autoimmunity in type 1 diabetes. / Ocaña, Gail J.; Sims, Emily K.; Watkins, Renecia A.; Ragg, Susanne; Mather, Kieren; Oram, Richard A.; Mirmira, Raghu; DiMeglio, Linda; Blum, Janice; Evans-Molina, Carmella.

In: PLoS One, Vol. 14, No. 1, e0208456, 01.01.2019.

Research output: Contribution to journalArticle

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