Human leukocyte antigen serologic and DNA typing of Behçet's disease and its primary association with B51

Area of Science:

• Immunogenetics
• Rheumatology
• Ophthalmology

Background:

• Behçet's disease (BD) is a multisystem inflammatory disorder with complex genetic associations.
• Human Leukocyte Antigen (HLA) genes, particularly class I and II, are implicated in autoimmune diseases.
• Previous studies suggest HLA associations with BD, but the precise genetic loci remain debated.

Purpose of the Study:

• To investigate the association of HLA class I and II alleles with Behçet's disease in a Japanese cohort.
• To identify specific HLA alleles linked to BD susceptibility, especially ocular manifestations.
• To determine the primary genetic locus responsible for BD pathogenesis.

Main Methods:

• Ninety Japanese BD patients and controls underwent conventional serologic HLA typing for HLA-A, -B, -C, -DR, and -DQ.
• Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for high-resolution HLA-DRB1, -DQA1, -DQB1, and -DPB1 genotyping.
• Statistical analysis, including chi-squared tests and relative risk calculations, was performed to assess allele frequencies.

Main Results:

• Serologic typing revealed a significant increase in HLA-B51 (RR=7.9) and a decrease in HLA-DQw1 (RR=0.4) in BD patients, especially those with ocular lesions.
• PCR-RFLP identified significantly higher frequency of DRB1*0802 and lower frequencies of DQA1*0103, DQB1*0601, and DQB1*0501 in BD patients, though not significant after correction.
• No significant differences were found in HLA-DPB1 alleles between groups.

Conclusions:

• The primary genetic susceptibility for Behçet's disease, particularly ocular involvement, appears strongly linked to the HLA-B locus (class I), not the HLA class II region.
• The findings suggest that HLA-B51 is a major susceptibility gene for BD.
• BD might represent a complex of symptoms associated with independent underlying diseases.