title: Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients.
abstract: OBJECTIVE
  Type 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells.
  
  
  METHODS
  We used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples.
  
  
  RESULTS
  We identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p = 1.17 × 10(-3)). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p = 4.8 × 10(-3)).
  
  
  CONCLUSIONS
  The 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients.
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0XY, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Downes
authors.forename: M Loredana
authors.initials: ML
authors.lastname: Marcovecchio
authors.forename: Pamela
authors.initials: P
authors.lastname: Clarke
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Ferreira
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jolley
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Helen E
authors.initials: HE
authors.lastname: Stevens
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: Chris
authors.initials: C
authors.lastname: Wallace
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D002096:C-Peptide; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit