Autoantibodies to a 38-kDa glycosylated islet cell membrane-associated antigen in (pre)type 1 diabetes: association with IA-2 and islet cell autoantibodies.
OBJECTIVE
To study the association of autoantibodies against a 38-kDa glycated islet cell membrane-associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification.


METHODS
Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays.


RESULTS
GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for > or = 1 other autoantibody.


CONCLUSIONS
GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs.
Winnock
F
F
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Christie
M R
MR
Batstra
M R
MR
Aanstoot
H J
HJ
Weets
I
I
Decochez
K
K
Jopart
P
P
Nicolaij
D
D
Gorus
F K
FK
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D001530:Belgium; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006031:Glycosylation; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011237:Predictive Value of Tests; D012042:Registries; D012727:Sex Characteristics
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C096322:ICA512 autoantibody; C024211:islet cell antibody; D005968:Glutamate Decarboxylase