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author:("van holter, J")
1.  Expression of interferon ß in synovial tissue from patients with rheumatoid arthritis: comparison with patients with osteoarthritis and reactive arthritis 
Annals of the Rheumatic Diseases  2005;64(12):1780-1782.
Objective: To determine the expression of IFNß in the synovial tissue of patients with RA, osteoarthritis, and reactive arthritis.
Methods: Synovial biopsy specimens were obtained by arthroscopy from patients with RA and disease controls for immunohistological analysis using a monoclonal antibody specific for IFNß. Bound antibody was detected by an immunoperoxidase method. Stained sections were evaluated by computer assisted image analysis. Double stainings were performed with antibodies to detect CD55 positive fibroblast-like synoviocytes (FLS), CD68 positive macrophages, and CD83 positive dendritic cells (DCs) coexpressing IFNß.
Results: IFNß protein was abundantly expressed in the synovium of patients with RA. Digital image analysis showed a significant increase in the mean integrated optical density for IFNß expression in RA synovial tissue compared with disease controls. Specific up regulation of IFNß expression was also seen when the results were controlled for cell numbers. Phenotypic analysis showed that FLS, especially, but also macrophages and DCs may express IFNß in RA synovial tissue.
Conclusions: The increased expression of IFNß in RA synovium suggests activation of an immunomodulatory mechanism that could inhibit synovial inflammation.
PMCID: PMC1755294  PMID: 15878901
2.  A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis 
Objective: To assess the efficacy of interferon beta (IFNß) in combination with methotrexate in treatment of patients with rheumatoid arthritis.
Methods: 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFNß 2.2 µg (0.05 ml), or IFNß 44 µg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study.
Results: Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFNß treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups.
Conclusions: At the doses tested, treatment with IFNß three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.
PMCID: PMC1755211  PMID: 15242865

Results 1-5 (5)