title: Soluble HLA-DR levels in serum are associated with therapy and genetic factors in rheumatoid arthritis.
abstract: 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.
authors.affiliation: From the Rheumatology Unit, Academical Hospital VUB, Brussels, Belgium. leon.verbruggen@az.vub.ac.be
authors.forename: Leon A
authors.initials: LA
authors.lastname: Verbruggen
authors.forename: Hendrik
authors.initials: H
authors.lastname: Versaen
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
authors.forename: William
authors.initials: W
authors.lastname: Duquet
authors.forename: Seija
authors.initials: S
authors.lastname: De Cock
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
authors.forename: Christian
authors.initials: C
authors.lastname: Demanet
mesh_terms: 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
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000939:Epitopes; D006684:HLA-DR Antigens; D011239:Prednisolone; D008727:Methotrexate