HLA class II genes in Graves' disease

Area of Science:

• Immunogenetics
• Molecular Biology
• Autoimmune Diseases

Background:

• The human leukocyte antigen (HLA) -DR3 gene product is associated with Graves' disease.
• The HLA-DR3 gene may play a role in antigen presentation, a key process in immune responses.

Purpose of the Study:

• To investigate if the first extracellular domain of the HLA-DR3 gene product has sequence variations in Graves' disease patients compared to healthy individuals.
• To determine the specific genetic sequences of HLA-DRB1 and HLA-DRB3 in patients with autoimmune thyroid disease.

Main Methods:

• Polymerase chain reaction (PCR) was used to amplify the second exon of the HLA-DRB gene.
• DNA sequencing was performed on the amplified gene segments.
• Genetic sequences were compared between Graves' disease patients and normal individuals.

Main Results:

• Sequences identical to the prototypic DRB1*0301 were found in most Graves' disease patients.
• Minor nucleotide variations leading to 1-3 amino acid substitutions were observed in some patients, but without a discernible pattern.
• Sequences identical to DRB3*0101 (formerly DRw52) were also identified.

Conclusions:

• The HLA-DRB1 and HLA-DRB3 genes in patients with Graves' disease are similar to those in the general population.
• No unique genetic allele was identified in patients, suggesting the standard DR3 allele confers increased susceptibility.
• The normal DR3 allele, through an as-yet-undescribed mechanism, appears to elevate the risk of developing autoimmune thyroid disease.