HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus.
The differential antibody response to glutamic acid decarboxylase (anti-GAD) and to islet cell cytoplasm (ICA) according to HLA-DR and DQ genotypes were examined in 28 Spanish patients with Type I diabetes mellitus (11.1 +/- 10.4 year diabetes duration) and their 41 first degree non-diabetic relatives. Anti-GAD was detected by radioimmunoprecipitation and ICA by indirect immunofluorescence and HLA-DR/DQ alleles were assigned by PCR and sequence specific oligonucleotide probes. The frequency in patients of positivity for ICA was 7.1% and of anti-GAD+ 64.3%, and in relatives, the frequency of ICA+ was 4.9%, and anti-GAD+ 9.8%. Concurrent positivity for ICA and anti-GAD existed in only one patient, and in none of the relatives. We confirm for a Spanish population the high frequency of risk genotypes for Type I, involving DR3, DR4 and DQB1*0302 (DQ8) which were present in 26 of 28 (93%) patients and 32 of 41 (78%) relatives. The most frequent genotypes were DR3/DQB1*0201/DQA1*0501-DR4/DQB1*0302/DQA1*0301( 9 patients, 32%; 6 relatives, 15%), DR3/DQB1*0201/ DQA1*0501-DR3/DQB1*0201/DQA1*0501 (5 patients, 18%; 7 relatives, 17%) and DE3/DQB1*0201/DQA1*0501-DR1/ DQB1*0501/DQA1*0101(5 patients, 18%; 1 relative, 2%). Positivity for anti-GAD or for ICA did not correlate with gender, or age at onset or duration of DM. The distribution of high risk HLA genotypes were similar regardless the anti-GAD or anti-ICA status either in patients or in their relatives.
Serrano-Ríos
M
M
Laboratorio de Lipidos y Diabetes, Hospital Clinico San Carlos, Madrid, Spain.
Gutierrez-López
M D
MD
Pérez-Bravo
F
F
Martínez
M T
MT
Antona
J
J
Rowley
M
M
Mackay
I
I
Zimmet
P
P
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005190:Family; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011233:Precipitin Tests; D013030:Spain; D013552:Swine / Q000276:immunology
D015415:Biomarkers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007106:Immune Sera; D005968:Glutamate Decarboxylase