Which HLA allele is associated with prognosis in rheumatoid arthritis?

• A. HLA-DR2
• B. HLA-DR4
• C. HLA-DR3
• D. HLA-DR1

Answer: (B)

Genetic factors, especially HLA-DRB1 alleles that carry the shared epitope, help determine how aggressively rheumatoid arthritis will behave. The shared epitope is a specific sequence motif in the HLA-DR beta chain that several alleles carry, with HLA-DRB1*04 (HLA-DR4) being the most classically linked to worse disease outcomes. People with these alleles tend to have more rapid radiographic progression and more severe joint damage over time, partly because these HLA molecules present arthritogenic peptides to CD4+ T cells more effectively, driving stronger autoimmunity and inflammation. This is why HLA-DR4 is recognized as associated with prognosis in rheumatoid arthritis. While other alleles can influence susceptibility or disease features in various populations, DR4 is the best-established marker for predicting a poorer prognosis.