Körmendy, Dezsö (2013). Impact of the CTLA-4/CD28 axis on the processes of joint inflammation in rheumatoid arthritis. Arthritis & rheumatism, 65(1), pp. 81-87. Wiley-Blackwell 10.1002/art.37714
Full text not available from this repository. (Request a copy)OBJECTIVE:
The importance of the costimulatory molecules CD28 and CTLA-4 in the pathologic mechanism of rheumatoid arthritis (RA) has been demonstrated by genetic associations and the successful clinical application of CTLA-4Ig for the treatment of RA. This study was undertaken to investigate the role of the CTLA-4/CD28 axis in the local application of CTLA-4Ig in the synovial fluid (SF) of RA patients.
METHODS:
Quantitative polymerase chain reaction was used to analyze the expression of proinflammatory and antiinflammatory cytokines in ex vivo fluorescence-activated cell sorted CTLA-4+ and CTLA-4- T helper cells from the peripheral blood and SF of RA patients. T helper cells were also analyzed for cytokine expression in vitro after the blockade of CTLA-4 by anti-CTLA-4 Fab fragments or of B7 (CD80/CD86) molecules by CTLA-4Ig.
RESULTS:
CTLA-4+ T helper cells were unambiguously present in the SF of all RA patients examined, and they expressed increased amounts of interferon-γ (IFNγ), interleukin-17 (IL-17), and IL-10 as compared to CTLA-4- T helper cells. The selective blockade of CTLA-4 in T helper cells from the SF in vitro led to increased levels of IFNγ, IL-2, and IL-17. The concomitant blockade of CD28 and CTLA-4 in T helper cells from RA SF by CTLA-4Ig in vitro resulted in reduced levels of the proinflammatory cytokines IFNγ and IL-2 and increased levels of the antiinflammatory cytokines IL-10 and transforming growth factor β.
CONCLUSION:
Our ex vivo and in vitro results demonstrate that the CTLA-4/CD28 axis constitutes a drug target for not only the systemic, but potentially also the local, application of the costimulation blocking agent CTLA-4Ig for the treatment of RA.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology |
UniBE Contributor: |
Körmendy, Dezsö |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0004-3591 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Dezsö Körmendy |
Date Deposited: |
03 Mar 2014 12:04 |
Last Modified: |
05 Dec 2022 14:28 |
Publisher DOI: |
10.1002/art.37714 |
PubMed ID: |
23045162 |
URI: |
https://boris.unibe.ch/id/eprint/41940 |
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