Circulating antibodies to nephrin in patients with type 1 diabetes.

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.

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