Soluble HLA-DR levels in serum are associated with therapy and genetic factors in rheumatoid arthritis.
As rheumatoid arthritis (RA) is an HLA-DR associated autoimmune disease and soluble HLA-DR (sHLA-DR) molecules have the capacity to regulate the immune response, we studied the sHLA-DR levels in RA patients in view of therapy modalities and clinical and biologic parameters of disease activity. For this sHLA-DR concentrations from 87 RA patients were determined by a sensitive enzyme-linked immunoabsorbent assay (ELISA) format. There was a weak but significant correlation between sHLA-DR levels and disease activity (r 0.186 to 0.287, p < 0.004 to < 0.001). The mean serum sHLA were not significantly different between groups with or without corticosteroids, or undergoing therapy with different disease modifying antirheumatic drugs. However, patients treated with a combination of methotrexate and prednisolone have lower sHLA-DR (206 +/- 21 ng/ml, n = 34) compared with the mean value for all other samples (306 +/- 16, n = 217, p < 0.001). This corresponded with significantly lower EULAR pain and swelling scores, ESR and rheumatoid factor (RF) by latex fixation (p < 0.02 to 0.001) in the former, compared with the latter group. Furthermore, sHLA-DR was, respectively, 267 +/- 15 ng/ml (n = 182) in samples from patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), and 358 +/- 31 (n = 72) without NSAIDs (p < 0.01). Lower sHLA-DR with NSAIDs contrasted with significantly higher scores for pain, swelling, CRP, and RF by latex fixation and by Waaler-Rose test (p < 0.05 to 0.001). Comparison of subgroups with or without the shared epitope of RA disease (Q)R/KRAA within the HLA-DR beta1-chain confirmed significantly higher parameters of disease activity and sHLA-DR in the presence of this disease associated epitope in our patients. Different mechanisms appear to be involved in sHLA-DR production or release, as their level correlates positively with disease activity under combined therapy with corticosteroids and methotrexate, but decreases with higher disease activity in patients treated with NSAIDs.
Verbruggen
Leon A
LA
From the Rheumatology Unit, Academical Hospital VUB, Brussels, Belgium. leon.verbruggen@az.vub.ac.be
Versaen
Hendrik
H
Rebmann
Vera
V
Duquet
William
W
De Cock
Seija
S
Grosse-Wilde
Hans
H
Demanet
Christian
C
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000235:genetics; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012995:Solubility
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000939:Epitopes; D006684:HLA-DR Antigens; D011239:Prednisolone; D008727:Methotrexate