HOMOZYGOSITY FOR THE DRB1(Q)R/KRAA CASSETTE AND GENETIC RISK AND DISEASE
SEVERITY AMONG COMMUNITY BASED RHEUMATOID ARTHRITIS.
C Seidl1, U Käßer2, U Koch2,3,
B Fischer1, L Meier2, P Fischer2, G Bach2,
G Faust-Tinnefeldt2, D Maas2, W Bolten2,
E Seifried1, JP Kaltwasser2,3. 1Institute
of Transfusion Medicine and Immunohematology, RCBDS; 2Rhein-Main
Center of Rheumatology, Frankfurt-Wiesbaden-Schlangenbad and 3the
Department of Rheumatology, Center of Internal Medicine, JW Goethe-University
Frankfurt, Germany.
In the present study we have analysed the effect of HLA-DRB1
alleles on disease activity and genetic predisposition among 162 ACR defined
RA patients. DRB1 typing was performed by PCR-SSP and shared epitope (Q)R/KRAA
positive alleles were defined by sequence based typing (Perkin Elmer, ABD
373A). Mean disease duration was 13.3 + 8.9 years (range 1-41). Patients
were grouped according to the presence of articular versus extraarticular
symptoms (nodules, vasculitis, pulmonary affection, Felty/Sicca syndrome).
Radiological destruction and functional health status was assessed among
140 patients by the Larsen score (LS) and HAQ score. Our results clearly
confirm the association of RA with the (Q)R/KRAA motif. Both, the LS in
(Q)R/KRAA homozygous patients and the HAQ score in (Q)R/KRAA positive patients
was increased by 25% (p<0.05) compared to (Q)R/KRAA negative patients.
However, homozygosity for the shared (Q)R/KRAA motif was only marginally
increased among patients presenting 'severe' extraarticular disease in
comparison to patients with articular disease (43% versus 33%, p=ns). In
conclusion, the (Q)R/KRAA cassette is associated with worse functional
status, the absolute worsening in outcomes in long-standing RA however
is small, making it of limited use as a predictor of prognosis.