THE SHARED EPITOPE INFLUENCES THE EXTENT AND PROGRESSION OF RHEUMATOID
ARTHRITIS.
A. Valenzuela, M.F. González-Escribano, R. Rodriguez,
K. Walter, I. Moreno, B. Sanchez, A. Garcia & A. Nuñez-Roldan.
Servicios de Inmunología and Reumatologia. Hospital
Universitario Virgen del Rocío. Servicio Andaluz de Salud. 41013.
Sevilla. Spain. Susceptibility to rheumatoid arthritis (RA) has been classically
associated with the inheritance of a shared epitope (SE) encoded by several
different MHC class II alleles. This epitope encompasses the sequences
LQRA, LQKA, or LRRA at positions 67, 70, 71, and 74, in HVR3 of the DRb1
first domain. In the last few years some discussion has emerged around
the role of the SE in RA severity and progression, rather than in disease
susceptibility. To get more insight into this question, a 8 year prospective
study was performed on 82 unrelated Spanish RA patients with a disease
duration of less than two years at the moment of the study entry. Fourteen
patients carried two SE+ HLA-DRB1 alleles (SE +/+); 36, one single allele
(SE +/-) and 32 were SE negative (SE -/-). Radiological evaluation of disease
severity was performed at the time of diagnosis and 5 and 8 years later
at study entry, the frequencies of locally severe (hands and feet) RA were:
79%, 44% and 44% among SE +/+, SE +/- and SE -/- patients respectively
(p=0.05; RR=1.8; 95% CI: 1.11-2.9 and p=0.05; RR=1.78; 95% CI: 1.12-2.8,
respectively). As disease progresses, these differences disappear whereas
differences in the extent of the disease arise: after 8-10 years of disease
outcome, 79%, 49% and 32% of SE +/+, SE +/- and SE -/- patients respectively
showed large joints involvement (shoulders, elbows, hips and knees) (p=0.01;
RR=2.44; 95% CI: 1.37-4.35). These results suggest that the presence of
the shared epitope is associated with the extent and progression of rheumatoid
arthritis.