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


CONCLUSIONS
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.
Walker
J G
JG
Repatriation General, Hospital, Daws Road, Daw Park 5041, South Australia, Australia.
Ahern
M J
MJ
Coleman
M
M
Weedon
H
H
Papangelis
V
V
Beroukas
D
D
Roberts-Thomson
P J
PJ
Smith
M D
MD
D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D053616:Janus Kinase 3 / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism*; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D050791:STAT Transcription Factors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D053616:Janus Kinase 3