Soluble HLA-G in rheumatoid arthritis.
We investigated potential correlations between soluble HLA-G (sHLA-G) and soluble HLA class I (sHLA-I) levels, respectively, and parameters of disease activity or genetic factors determined by HLA-DRB1 and HLA-DQB1 in patients with rheumatoid arthritis (RA). SHLA-G plasma concentrations from 106 RA patients (mean age 59.8 years, 80 women) were assessed by a sensitive enzyme-linked immunosorbent assay format. The mean sHLA-G levels were lower and sHLA-I levels higher in the RA patients than in healthy controls. Correlation coefficients of 0.248 to 0.344 (p < 0.01) between sHLA-G and rheumatoid factor, CRP, and EULAR joint swelling score were found. Patients with disease-associated HLA epitopes had higher sHLA-G levels than those without. Significantly lower sHLA-G was observed in groups of patients having HLA-DRB1*03 or HLA-DQB1*02 compared to groups without these genotypes. In contrast, HLA-DQB1*03 or disease-associated epitopes combined with HLA-DQB1*03 were associated with higher sHLA-G levels, whereas the inverse was observed in the combined presence of HLA-DRB1*03 and HLA-DQB1*02. SHLA-G as a percentage of sHLA-I was lower in patients positive for HLA-DQB1*02 and higher in patients positive for HLA-DQB1*03 and in its combined presence with disease-associated epitopes or with HLA-DRB1*07. As especially sHLA-G strongly inhibits T and natural killer (NK) cell functions, low sHLA-G suggests that T and NK cell activities are not efficiently restricted by sHLA-G molecules in rheumatoid arthritis. The sHLA-G levels, however, increase in correlation with parameters of disease activity and appear to be affected by the presence of disease-predisposing epitopes and other HLA-DRB1, DQB1 genotypes.
Verbruggen
Leon A
LA
Rheumatology Unit, Academical Hospital Vrije Universiteit Brussel, Brussels, Belgium. leon.verbruggen@az.vub.ac.be
Rebmann
Vera
V
Demanet
Christian
C
De Cock
Seija
S
Grosse-Wilde
Hans
H
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000097:blood*; D006683:HLA-DQ Antigens / Q000097:blood; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000097:blood; D059811:HLA-DRB1 Chains; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged
D000939:Epitopes; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins