Sitelbanat Awadalla and Manan AL Hakbany
The screening of non-diabetic siblings of Saudi type 1 diabetes mellitus (T1DM) patients (n=54) and 50 healthy controls was undertaken for glutamic acid decarboxylase (anti-GAD) and antibodies to tyrosine phosphatse (IA-2) using radioimmunoprecipitation. HLA-DRB1, DQB1 and DQA1 alleles were tested by PCR and sequence-specific oligonucleotide probes. HLA analysis showed that susceptible alleles were DRB1*03:01 (61.1%) *04:01 (22.02%), DQA1*05:01 (61.1%), DQA1*03:03 (33.3%) and DQB1*02:01 (72.2%). The DRB1*03:01-DQA1*05:01-DQB1*02:01 haplotype was significantly higher among siblings (61%). The protective alleles were DRB1*04:03 (1.8%), DRB1*13 (11.1%), DQA1*02:01 (5.6%), DQA1*05:05 (5.6%), DQB1*03:01 (5.6%) and DQB1*05:01 (11.1%). GADA (22.2%) and anti-IA-2 (11.1%) were significantly higher among siblings, both antibodies present in 27.8% of siblings. The frequency of GADA was higher in those aged 5 to 10 years (50%), while IA-2 positive children were > 5years old (100%). 36.4 % of DRB1*03:01-DQA1*05:01-DQB1*02:01 sibling were positive for GADA, 18.2% were positive for IA-2 and 9.1% were positive for both antibodies. 27.8% of siblings were HLA-identical to the proband, 61.1% were haploidentical, and 11.1% were not identical. GADA was significantly higher among the HLA-identical siblings (60%) than haploidentical (9.1%) and non-identical siblings (zero). IA-2 was higher in HLA-identical (20%) from haploidentical (9.1%) and non-identical HLA (zero) but not to significant level. Both antibodies were present in 20% of HLA-identical siblings, and in none of the haplo- or non-identical HLA. In conclusion, the immunogenetic screening of nondiabetic sibling identifies individuals at risk of developing T1DM.