Endocrine Abstracts

Introduction: Polyglandular autoimmune syndrome (PAS) are uncommon constellations of autoimmune diseases characterized by the occurrence of two or more auto-immune endocrine diseases in the same individual.

Patients and methods: It is a case-control study about 108 cases for 120 healthy subjects recruited as the control group. We aimed to study the polymorphism of the HLA class-II genes of patients compared to that of healthy subjects so as to identify the genetic susceptibility to PAS.

Results: Among 108 patients, 2 patients had PAS type I (PAS-I), 39 patients had the type II (PAS-II) and 67 patients had the type III (PAS-III). Thirteen patients with PAS-II against 120 healthy subjects in the control group were included for the genetic testing of HLA class-II allele. DRB1*03 allele was associated with the occurrence of PAS-II whereas DRB1*13 was detected in only one patient but in 40 subjects expressing a negative association of this allele with PAS-II but remains statistically insignificant. We also found the association of DQB1*0302 in our population (P=0.004). DQB1*06 is a protective allele more prevalent in healthy subjects (22.97%) than in patients (3.8%) (P=0.023) but this difference becomes insignificant after Bonferroni correction. Twenty-seven patients with PAS-III were tested for HLA class-II alleles. DRB1*03 allele was found to be associated with PAS-III (P=0.0001) whereas no association was noted with DRB1*04 allele (P=0.22). DRB1*13 allele was found in 5 patients and 40 subjects in favor of the negative association of this allele in PAS-III (P=0.11). A significant association was also observed with DQB1*02 allele in our population (P=0.0034). In all, 40 patients with PAS-II/III were tested for HLA class-II alleles and demonstrated the association of PAS-II/III with DRB1*03 allele (P=0.0021) but a less significant association was noted with DRB1*04 (P=0.05). As far as protective DRB1*13 and DQB1*06 alleles are concerned, we noticed a negative association but insignificant after correction in PAS.

Discussion and Conclusion: The genetics of PAS is based essentially on the association of certain alleles of the human major histocompatibility complex. The presence of susceptibility alleles DRB1*03 and DQB1*0302 is described in literature. However, some studies showed the association of DR4-DQB1*0302 with PAS-II or III is due entirely to the presence of pancreatic auto-antibodies whereas haplotype DR3-DQB1*0201 is associated not only with type-1 diabetes mellitus but also PAS-II/III in the absence of pancreatic autoantibodies. The study of genetics have evolved considerably during the last years, especially due to molecular biology techniques.