Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes.
OBJECTIVE
The development of autoantibodies against antigens of the pancreatic islet cells is a typical phenomenon in patients with type 1 diabetes. The expression of densin, recently shown to be present in kidney podocytes, was explored in the pancreas. Additionally, we studied whether densin and filtrin, another molecule shared between the kidney podocytes and pancreatic islet cells, can act as autoantigens and whether autoantibodies against these can be detected in patients with type 1 diabetes.


METHODS
Expression of pancreatic densin was studied with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence. Children and adolescents (n = 66) with type 1 diabetes and control subjects were analysed for densin autoantibodies (DAA) and filtrin autoantibodies (FAA) using radioimmunoprecipitation assay. The serum samples were obtained at the time of diagnosis and after a duration of 2, 5 and 10 years.


RESULTS
Densin expression was observed in the pancreas, localising to the beta cells. DAA were detected in 33% of the patients and the positivity was typically seen already at diagnosis. FAA were observed in 11% of the patients. The proportion of islet cell antibody (ICA) positive, GADA positive and protein tyrosine phosphatase-related islet antigen 2 antibody (IA-2A)-positive patients decreased during the follow-up period, and a similar trend was seen for DAA but not for FAA. Among the 14 patients with signs of renal injury, four tested positive for DAA and two for FAA.


CONCLUSIONS
Densin is a novel molecule shared by the kidney glomerular podocytes and pancreatic islet cells. Densin and filtrin can act as autoantigens, and autoantibodies against these can be detected in patients with type 1 diabetes.
Rinta-Valkama
Johanna
J
Biomedicum Helsinki, Department of Bacteriology and Immunology, University of Helsinki, Finland.
Aaltonen
Petri
P
Lassila
Markus
M
Palmén
Tuula
T
Tossavainen
Päivi
P
Knip
Mikael
M
Holthöfer
Harry
H
D000293:Adolescent; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001794:Blood Pressure; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis* / Q000276:immunology; D007668:Kidney / Q000276:immunology*; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology; D010179:Pancreas / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay; D012795:Sialoglycoproteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D006442:Glycated Hemoglobin; D007136:Immunoglobulins; D008565:Membrane Proteins; D012795:Sialoglycoproteins; C482646:KIRREL2 protein, human; C504461:LRRC7 protein, human