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NDT Advance Access originally published online on September 8, 2006
Nephrology Dialysis Transplantation 2007 22(1):146-153; doi:10.1093/ndt/gfl486
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Circulating antibodies to nephrin in patients with type 1 diabetes

Petri Aaltonen1, Johanna Rinta-Valkama1, Anu Pätäri1, Päivi Tossavainen2, Tuula Palmén1, Petri Kulmala2, Mikael Knip3 and Harry Holthöfer1

1Department of Bacteriology and Immunology, University of Helsinki, 2Department of Pediatrics, University of Oulu and 3Hospital for Children and Adolescents, University of Helsinki, Finland

Correspondence and offprint requests to: Harry Holthöfer, MD, PhD, Biomedicum, MolecularMedicine, PB 63, 00014 University of Helsinki, Finland. Email: Harry.Holthofer{at}Helsinki.Fi



  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 ß-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.

Keywords: autoimmunity; diabetic nephropathy; nephrin; radioimmunoprecipitation; type 1 diabetes


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