title: Circulating antibodies to nephrin in patients with type 1 diabetes.
abstract: BACKGROUND
  Patients with type 1 diabetes typically develop autoantibodies to antigens of the pancreatic islet cells including insulin, glutamic acid decarboxylase and the protein tyrosine phosphatase-related islet antigen 2 protein. Nephrin is a protein shared by the kidney glomeruli, pancreatic beta-cells and islet microendothelia. Since circulating antibodies to nephrin have been shown to cause proteinuria, we wanted to test whether such autoantibodies can be detected in diabetic patients.
  
  
  METHODS
  We developed a radioimmunoprecipitation assay and analysed samples in a follow-up series of 66 patients with type 1 diabetes.
  
  
  RESULTS
  A total of 24% of the patients tested positive for nephrin autoantibodies at diagnosis, whereas 23, 14 and 18% had these antibodies at 2, 5 and 10 years, respectively. During the follow-up at 16-19 years after diagnosis, 14 patients had signs of renal injury and 29% of them tested positive for nephrin autoantibodies in at least one sample.
  
  
  CONCLUSIONS
  We conclude that a subset of patients with type 1 diabetes present with circulating autoantibodies to nephrin. However, the present data do not allow conclusions of a causative role for these antibodies in the pathogenesis of proteinuria in diabetes.
authors.affiliation: Biomedicum, MolecularMedicine, PB 63, 00014 University of Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Aaltonen
authors.forename: Johanna
authors.initials: J
authors.lastname: Rinta-Valkama
authors.forename: Anu
authors.initials: A
authors.lastname: Pätäri
authors.forename: Päivi
authors.initials: P
authors.lastname: Tossavainen
authors.forename: Tuula
authors.initials: T
authors.lastname: Palmén
authors.forename: Petri
authors.initials: P
authors.lastname: Kulmala
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Harry
authors.initials: H
authors.lastname: Holthöfer
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D007223:Infant; D007668:Kidney / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000737:chemistry* / Q000276:immunology*; D008856:Microscopy, Fluorescence; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D008565:Membrane Proteins; C113267:nephrin