Why CCR2 and CCR5 Blockade Failed in Rheumatoid Arthritis
Author Information
Author(s): Maria C. Lebre, Clarissa E. Vergunst, Ivy Y. K. Choi, Saïda Aarrass, Ana S. F. Oliveira, Tim Wyant, Richard Horuk, Kris A. Reedquist, Paul P. Tak
Primary Institution: Academic Medical Center/University of Amsterdam
Hypothesis
Why blockade of CCR1, CCR2, and CCR5 may have failed in clinical trials in rheumatoid arthritis patients.
Conclusion
Blockade of CCR1 may be effective in inhibiting monocyte migration in rheumatoid arthritis, while CCR2 and CCR5 are not critical for this process.
Supporting Evidence
- Monocytes from RA patients showed different migration responses compared to healthy donors.
- Blocking CCR1 significantly reduced monocyte migration towards synovial fluid.
- CCR2 and CCR5 blockade did not inhibit migration induced by synovial fluid.
Takeaway
This study looked at why certain treatments for rheumatoid arthritis didn't work. It found that blocking one specific receptor (CCR1) might help, while blocking others (CCR2 and CCR5) didn't make a difference.
Methodology
Monocytes from healthy donors and RA patients were isolated and tested for migration in response to various chemokine receptor blockades.
Potential Biases
Potential bias due to the involvement of pharmaceutical companies in the study.
Limitations
The study was limited to in vitro models and may not fully represent in vivo conditions.
Participant Demographics
8 healthy donors and 21 rheumatoid arthritis patients, with a mean age of 56.1 to 60.2 years.
Statistical Information
P-Value
p=0.0005
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website