Spondyloarthropathies in eastern Asia

Area of Science:

• Immunogenetics
• Rheumatology
• Molecular Biology

Background:

• The Human Leukocyte Antigen B27 (HLA-B27) gene is strongly associated with spondyloarthropathies (SpAs), suggesting a pathogenic role for the HLA-B27 molecule.
• Global frequencies of HLA-B27 and its subtypes vary significantly, correlating with differing SpA prevalence across populations (e.g., Whites, Chinese, Japanese, Indonesians).

Purpose of the Study:

• To investigate the differential association of HLA-B27 subtypes with SpA across diverse ethnic groups.
• To identify specific molecular differences in HLA-B27 subtypes that may explain variations in SpA pathogenesis and clinical presentation.

Main Methods:

• Analysis of HLA-B27 subtype distribution in SpA patients and healthy individuals across different global populations.
• Comparison of amino acid sequences of SpA-associated and non-associated HLA-B27 subtypes, focusing on the peptide-binding groove.

Main Results:

• While HLA-B27 is prevalent in many populations, SpA is rare in native Indonesians, who predominantly carry the B*2706 subtype, which is not associated with SpA.
• The SpA-associated subtypes differ from non-associated ones (like B*2706) by only two amino acid residues at positions 114 and 116 in the peptide-binding groove.
• HLA-B27 subtyping is crucial for clinical utility in Southeast Asia, unlike in regions where B*2706 is rare. Juvenile SpA is common in Chinese populations.

Conclusions:

• The specific amino acid variations within HLA-B27 subtypes significantly influence SpA association, highlighting the importance of peptide-binding groove interactions in disease pathogenesis.
• Clinical implications include the necessity of HLA-B27 subtyping for accurate diagnosis in certain ethnic groups, particularly in Southeast Asia.