HLA-DR, DQ AND ANTI-GAD ANTIBODIES IN FIRST DEGREE RELATIVES OF TYPE-I DIABETES-MELLITUS

The differential antibody response to glutamic acid decarboxylase (ant i-GAD) and to islet cell cytoplasm (ICA) according to HLA-DR and DQ ge notypes were examined in 28 Spanish patients with Type I diabetes mell itus (11.1 +/- 10.4 year diabetes duration) and their 41 first degree non-diabetic relatives. Anti-GAD was detected by radioimmunoprecipitat ion and ICA by indirect immunofluorescence and HLA-DR/DQ alleles were assigned by PCR and sequence specific oligonucleotide probes. The freq uency 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 on e patient, and in none of the relatives. We confirm for a Spanish popu lation the high frequency of risk genotypes for Type I, involving DR3, DR4 and DQB10302 (DQ8), which were present in 26 of 28 (93%) patient s and 32 of 41 (78%) relatives. The most frequent genotypes were DR3/D QB10201/DQA1*0501-DR4/DQB1*0302/DQA1*0301 (9 patients, 32%; 6 relativ es, 15%), DR3/DQB10201/DQA1*0501-DR3/DQB1*0201/DQA1*0501 (5 patients, 18%; 7 relatives, 17%) and DR3/DQB10201/DQA1*0501-DR1/DQB1*0501/DQA1 0101 (5 patients, 18%; 1 relative, 2%). Positivity for anti-GAD or fo r 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 relativ es.