Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation.

@article{Vergunst2007BlockingTR,
  title={Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation.},
  author={Clarissa E. Vergunst and Danielle M. Gerlag and H. J. Dinant and L. Cl. Schulz and Marjolein Vinkenoog and T. J. M. Smeets and M E Sanders and Kris A. Reedquist and Paul P. Tak},
  journal={Rheumatology},
  year={2007},
  volume={46 12},
  pages={
          1773-8
        }
}
OBJECTIVES All complement pathways lead to the formation of C5a, which is believed to contribute to the influx and activation of C5a-receptor (C5aR) bearing cells into the joints of patients with rheumatoid arthritis (RA). Studies in animal models of RA have suggested therapeutic potential of C5aR blockade. In this study, we examined the effects of the C5aR blockade on synovial inflammation in RA patients. METHODS We performed a double-blind, placebo-controlled study using an orally… 
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Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial.
TLDR
The results do not support the notion that blockade of CCR2 may be sufficient to induce clinical improvement in RA, and treatment with anti-CCR2 blocking antibody did not result in amelioration of synovial inflammation in active RA.
C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid
TLDR
The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C 5a or C5 aR may be a promising treatment target in both diseases.
Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors.
Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis.
TLDR
It is suggested that CPB plays a critical role in dampening local, C5a-mediated inflammation and represents a molecular link between inflammation and coagulation in autoimmune arthritis.
Targeting Complement in Rheumatoid Arthritis
TLDR
A role for complement activation in the pathogenesis of this disease is supported by studies showing an association between complement activation and inflammatory responses in the diseased joints or in individual cell types found in RA joints, and by extensive studies on animal models of the disease.
Synovial Tissue Response to Treatment in Rheumatoid Arthritis
TLDR
The effects of RA treatments on the synovial tissue, including targeted therapies, are reviewed, with particular attention to their effect onsynovial biomarkers.
Receptors for complement C5a. The importance of C5aR and the enigmatic role of C5L2
TLDR
The development of effective mAbs to human C5aR to prevent disease onset and reverse established disease in the K/B × N arthritis model is tested.
C5a receptor enables participation of mast cells in immune complex arthritis independently of Fcγ receptor modulation.
TLDR
Stimulation via C5aR is required to unleash the proinflammatory activity of synovial mast cells in immune complex arthritis, albeit via a mechanism that is distinct from C 5a-modulated expression of FcγR.
The critical role of C5a as an initiator of neutrophil-mediated autoimmune inflammation of the joint and skin.
Interactions of the complement system with molecules of extracellular matrix: relevance for joint diseases.
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