Autoantibodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screening.
It has been reported that there is a heterogeneity in the clinical course of Japanese patients with type 1 diabetes. To elucidate the associations of expression of autoantibodies to multiple islet antigens with age of onset and mode of diagnosis of diabetes in Japanese patients with type 1 diabetes, autoantibodies against the protein tyrosine phosphatase-like molecules ICA512 (IA-2) and phogrin (IA-2beta) (ICA512/phogrin-A), GAD (GADA), insulin (IAA), and islet cell cytoplasm (ICA) were determined in sera from 73 Japanese patients with type 1 diabetes obtained within 14 days of diagnosis. Patients were divided into groups based on the age of onset (</=10 years, n=24 and >10 years, n=49) or the mode of onset (abrupt onset, n=59 and urinary screening identified, n=14). Of 73 new-onset patients with type 1 diabetes, 43 (59%) and 32 (44%) had ICA512A and phogrin-A levels exceeding the 99th percentile of 184 normal control subjects, respectively. Forty-five patients (62%) were positive for either ICA512A or phogrin-A. The frequencies for other autoantibodies were 71% for GADA, 48% for IAA, and 62% for ICA. The frequency of ICA512/phogrin-A was significantly higher in patients with an age of onset less than 10 years (83%) than in patients aged >10 years (51%, P<0.01). The positivity of ICA512/phogrin-A was less in patients whose diabetes was diagnosed by the urine glucose screening test (21%, P<0.001) than in abrupt onset patients (71%). Combined analysis (>/=1 antibody) of GADA, IAA, and ICA512/phogrin-A detected 88% of abrupt onset and 93% of screening-positive patients vs. 70% and 29%, respectively, for ICA (P<0.0005). These results indicate that the expression of ICA512/phogrin-A and cytoplasmic ICA is less in patients identified by urinary glucose testing but indicate that with combined autoantibody testing 90% of patients can be identified independent of the mode of diagnosis.
Sera
Y
Y
The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, 852-8501, Japan.
Kawasaki
E
E
Abiru
N
N
Ozaki
M
M
Abe
T
T
Takino
H
H
Kondo
H
H
Yamasaki
H
H
Yamaguchi
Y
Y
Akazawa
S
S
Nagataki
S
S
Uchigata
Y
Y
Matsuura
N
N
Eguchi
K
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006684:HLA-DR Antigens / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8
D001323:Autoantibodies; D001324:Autoantigens; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C516862:PTPRN protein, human; C102889:PTPRN2 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase