Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment

• Published in: Annals of the rheumatic diseases 2006-12, Vol.65 (12), p.1558-1564
• Main Authors: Walker, J G, Ahern, M J, Coleman, M, Weedon, H, Papangelis, V, Beroukas, D, Roberts-Thomson, P J, Smith, M D
• Format: Article
• Language: English
• Subjects: Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Biological and medical sciences; Biopsy; Cohort Studies; Cytokines; Dendritic cells; Diseases of the osteoarticular system; Down-Regulation - drug effects; Extended Report; Humans; Inflammation; Inflammatory joint diseases; Janus Kinase 3 - metabolism; Kinases; Medical sciences; Proteins; Rheumatism; Rheumatoid arthritis; Rheumatology; Severity of Illness Index; Signal transduction; STAT Transcription Factors - metabolism; STAT1 Transcription Factor - metabolism; STAT4 Transcription Factor - metabolism; STAT6 Transcription Factor - metabolism; Synovial Membrane - metabolism; Transcription factors; Treatment Outcome
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/ard.2005.050385

Background: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA). Objective: To examine the effect of successful disease-modifying antirheumatic drug (DMARD) treatment on the expression of Jak-STAT in a cohort of patients with active rheumatoid arthritis. Methods: Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry. Results: Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation. Conclusion: Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up-regulation of inhibitory pathways, or suppressing inflammatory paths.