Shared Epitope in RA — SCE Rheumatology MCQ

Correct answer: D — It is a five-residue motif at HLA-DRβ1 positions 70–74; *04:01 encodes QKRAA and is associated particularly with susceptibility to ACPA-positive RA.

Explanation lettering: E = shown as A · D = shown as B · B = shown as D · A = shown as E

The shared epitope is the classical QKRAA, QRRAA or RRRAA motif at residues 70–74 in the third hypervariable region of the HLA-DRβ1 chain; HLA-DRB1*04:01 encodes QKRAA. Shared-epitope alleles constitute a major genetic susceptibility factor for RA, especially ACPA-positive disease, plausibly through effects on peptide binding and presentation of citrullinated antigens. Modern fine-mapping shows that residues at positions 11/13, 71 and 74 refine susceptibility and outcome associations, so the classical motif is not a complete genetic model and does not deterministically predict severity. Its role in treatment-response prediction remains unestablished, excluding A. It is not a drug-metabolism locus (C), an HLA-B27 feature (D), or a neutral polymorphism (E). Routine HLA typing is not required for individual RA management.

Reference: RMD Open. HLA-DR risk variants in rheumatoid arthritis: what we know and still do not know. 2026. https://pubmed.ncbi.nlm.nih.gov/42161413/