Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease-associated epitopes.
We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.
Verbruggen
L A
LA
Rheumatology Unit, Academical Hospital, Free University Brussels, Belgium. reuvnl@az.vub.ac.be
Dumarey
N
N
Van de Velde
H
H
Rebmann
V
V
Flament
J
J
Van Wayenberge
C
C
Grosse-Wilde
H
H
Demanet
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood* / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D051381:Rats; D012995:Solubility
D018985:Epitopes, B-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains