HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus

• Published in: Diabetes research and clinical practice 1996-10, Vol.34, p.S133-S139
• Main Authors: SERRANO-RIOS, M, GUTIERREZ-LOPEZ, M. D, PEREZ-BRAVO, F, MARTINEZ, M. T, ANTONA, J, ROWLEY, M, MACKAY, I, ZIMMET, P
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Animals; Biological and medical sciences; Biomarkers - blood; Child; Child, Preschool; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Family; Female; Genotype; Glutamate Decarboxylase - immunology; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; Humans; Immune Sera - immunology; Islets of Langerhans - immunology; Male; Medical sciences; Middle Aged; Pedigree; Precipitin Tests; Spain; Swine - immunology
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(96)01316-2

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.