Statistics from Altmetric.com
In two papers, investigators from the Karolinska Institutet provide an exciting new perspective on the role of antibodies to citrullinated proteins (anticitrullinated protein antibodies or ACPA) in the pathogenesis of rheumatoid arthritis (RA).1 ,2 The data are intriguing and they point to unexpected mechanisms by which these autoantibodies may drive disease manifestations. By revealing a potential role of ACPA in the bone loss and pain that are cardinal features of RA, the investigative teams have advanced a new concept that may (same comment) account for the signs and symptoms of RA at the onset of synovitis as well as during the period of the most intense activity.
The first study by Krishnamurthy et al1 addressed the basis of RA bone loss. Building on prior research on effects of ACPA on bone,3 the study demonstrates that polyclonal ACPA derived from patients with RA as well as select monoclonal ACPA can induce osteoclastogensis in human monocytes in vitro. This process appears dependent on a combination of intracellular protein citrullination in the osteoclast as well as autocrine production of (interleukin 8) IL-8. Furthermore, in an animal model, the investigators show that intravenous administration of monoclonal ACPA can induce trabecular bone loss as measured by micro computed tomography (microCT). In this model, the administration of ACPA did not induce synovial inflammation, with the inhibition of bone loss by IL-8 blockade but not by tumour necrosis factor (TNF) blockade suggesting a mechanism for bone loss beyond inflammation.1
The second study by Wigerblad et al2 used similar reagents to explore the effects of ACPA on pain. As the results of the study show, the administration of either polyclonal human ACPA or murinised monoclonal ACPA derived from human RA synovium can induce both spontaneous and evoked pain behaviour in mice. This …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.