TY - JOUR
T1 - HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus
AU - Serrano-Ríos, M.
AU - Gutierrez-López, M. D.
AU - Pérez-Bravo, F.
AU - Martínez, M. T.
AU - Antona, J.
AU - Rowley, M.
AU - Mackay, I.
AU - Zimmet, P.
PY - 1996/10
Y1 - 1996/10
N2 - 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 DR3/DQB1*0201/DQA1*0501DR1/DQB1*0501/DQA1*0l01 (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 of the anti-GAD or anti-ICA status either in patients or in their relatives.
AB - 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 DR3/DQB1*0201/DQA1*0501DR1/DQB1*0501/DQA1*0l01 (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 of the anti-GAD or anti-ICA status either in patients or in their relatives.
KW - glutamic acid decarboxylase
KW - HLA/DR/DQ
KW - islet cell cytoplasm
KW - Spanish families
KW - type I (insulin-dependent) diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=19244381639&partnerID=8YFLogxK
U2 - 10.1016/S0168-8227(96)01316-2
DO - 10.1016/S0168-8227(96)01316-2
M3 - Article
C2 - 9015682
AN - SCOPUS:19244381639
VL - 34
SP - S133-S139
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
SN - 0168-8227
IS - SUPPL.
ER -