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NDT Advance Access published online on September 8, 2006
Nephrology Dialysis Transplantation, 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
Received March 3, 2006
Accepted July 20, 2006

Original Article

Circulating antibodies to nephrin in patients with type 1 diabetes

Petri Aaltonen 1, Johanna Rinta-Valkama 1, Anu Pätäri 1, Päivi Tossavainen 2, Tuula Palmén 1, Petri Kulmala 2, Mikael Knip 3, and Harry Holthöfer 1 *

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

* To whom correspondence should be addressed.
Harry Holthöfer, E-mail: 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 {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.

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