title: A drop in the circulating concentrations of soluble receptor for advanced glycation end products is associated with seroconversion to autoantibody positivity but not with subsequent progression to clinical disease in children en route to type 1 diabetes.
abstract: Advanced glycation end products (AGEs) and their interaction with the receptor for AGEs (RAGE) have been studied for their role in the pathogenesis and complications of type 1 diabetes. Decreased concentrations of soluble RAGE (sRAGE) have been reported in acute autoimmune inflammation. We set out to analyze the changes in sRAGE concentration during preclinical diabetes in children seroconverting to islet autoantibody positivity.
  
  
  
  We measured serum concentrations of sRAGE in 168 children who progressed to clinical disease and 43 children who turned positive for at least 2 diabetes-associated autoantibodies but remained nondiabetic. We analyzed the sRAGE before seroconversion in the first autoantibody-positive sample and annually thereafter until the diagnosis of type 1 diabetes or end of follow-up.
  
  
  
  Both groups had similar sRAGE before seroconversion, but subsequently, sRAGE concentrations were lower (P < .001) in the progressors. The progressors had significantly higher sRAGE concentrations before than after seroconversion (P < .001). The nonprogressors did not experience a similar decrease. The sRAGE concentrations remained stable after seroconversion in both groups.
  
  
  
  These data indicate that sRAGE may be involved in the initiation of beta-cell autoimmunity but not in the progression from beta-cell autoimmunity to clinical disease.
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: K M
authors.initials: KM
authors.lastname: Salonen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: S J
authors.initials: SJ
authors.lastname: Ryhänen
authors.affiliation: Glycation and Diabetes Group, Mater Research Institute, The University of Queensland Translational Research Institute, Brisbane, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Forbes
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Härkönen
authors.affiliation: Immunogenetics Laboratory, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.affiliation: Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Veijola
authors.affiliation: Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Devision of Nephrology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland.|Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: P-H
authors.initials: PH
authors.lastname: Groop
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.|Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Knip
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*; D011971:Receptors, Immunologic / Q000097:blood; D000069078:Seroconversion / Q000502:physiology*
chemical_list: D001323:Autoantibodies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
keywords: age; islet autoantibodies; seroconversion; soluble RAGE; type 1 diabetes