Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals.
The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS)
Thivolet
C H
CH
Department of Pediatrics, Edouard Herriot Hospital, Lyon, France.
Tappaz
M
M
Durand
A
A
Petersen
J
J
Stefanutti
A
A
Chatelain
P
P
Vialettes
B
B
Scherbaum
W
W
Orgiazzi
J
J
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005190:Family; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007515:Islets of Langerhans / Q000276:immunology; D008970:Molecular Weight; D011379:Prognosis; D012307:Risk Factors
D001323:Autoantibodies; D006684:HLA-DR Antigens; C024211:islet cell antibody; D005968:Glutamate Decarboxylase