Value of ICA512 antibodies for prediction and diagnosis of type 1 diabetes.
ICA512 was isolated from an islet cDNA expression library and was identified as transmembrane protein closely related to the T-cell tyrosine phosphatase CD45. In order to determine the frequency of antibodies (ab) to ICA512, we tested sera of 124 newly diagnosed type 1 diabetic patients (IDDM) and 30 patients with long standing IDDM, 44 non-diabetic first degree relatives (FDR) with positive ICA or IAA, and 76 healthy control subjects using an ELISA. The mean +/- SD that we obtained in our control population was 4.1 +/- 3.9 U and a cut-off of 16 U was defined as normal range (mean + 3 SD). Of newly diagnosed diabetic patients and patients with long standing IDDM, 32% and 23% respectively had positive ICA512-ab with a mean of 22 +/- 33 U (vs controls p < 0.001) and 14 +/- 14 U (p < 0.01). Of antibody-positive first degree relatives, 36% were found to have elevated ICA512-ab with a mean of 24 +/- 41 U (p < 0.01). In relatives with multiple follow-up samples, ICA512-ab were found to be constantly positive or negative in 86% of cases, whereas fluctuation of ICA512-ab positivity occurred in five relatives in which three developed positive ICA512-ab and two lost ICA512-ab positivity during follow-up. Of ICA512-ab + relatives, 76% progressed to clinical type 1 diabetes within 5 years of follow-up, whereas only 24% developed diabetes in the ICA512-ab negative group (p < 0.01). ICA512-ab were more frequent in newly diagnosed diabetic children below age 15 years (p < 0.02) and in patients with positive ICA (p < 0.001) or positive IAA (p < 0.02). There was, in contrast, no correlation of ICA512-ab with GADA. One patient with newly diagnosed type 1 diabetes exclusively exhibited ICA512-ab. In conclusion, these results suggest that ICA512-ab are related to autoimmune type 1 diabetes and useful as an additional screening marker for the prediction of type 1 diabetes.
Mayrhofer
M
M
Diabetes Research Institute, Academic Hospital Müchen-Schwabing, Germany.
Rabin
D U
DU
Messenger
L
L
Standl
E
E
Ziegler
A G
AG
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D015993:Life Tables; D008565:Membrane Proteins / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012016:Reference Values; D012307:Risk Factors
D001323:Autoantibodies; D001324:Autoantigens; D008565:Membrane Proteins; C024211:islet cell antibody; D017493:Leukocyte Common Antigens; C516862:PTPRN 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