PPAD remains a credible candidate for inducing autoimmunity in rheumatoid arthritis: comment on the article by Konig et al

Authors

Anne-Marie Quirke, University of Oxford
Karin Lundberg, Karolinska Institutet
Jan Potempa, Jagiellonian University
Ted R. Mikuls, University of Nebraska Medical Center
Patrick J. Venables, University of OxfordFollow

Date of this Version

2015

Citation

Quirke A-M, Lundberg K, Potempa J, et al. Ann Rheum Dis 2015;74:e7.

Comments

US government work.

Abstract

There is accumulating evidence that periodontitis is linked to rheumatoid arthritis (RA) and that this may be due to the pathogen Porphyromonas gingivalis possessing a peptidyl arginine deiminase (PPAD). This apparently unique bacterial enzyme is capable of producing citrullinated bacterial or host proteins which could break tolerance leading to the generation of autoantibodies in RA.¹ We have previously shown that PPAD is autocitrullinated and there is an increased antibody response to PPAD in RA, which was due to reactions with autocitrullinated epitopes on the PPAD molecule.² We were therefore interested to read the article by Konig et al³ in which they confirm our findings that full-length recombinant PPAD is autocitrullinated, but showed that a truncated and secreted form of PPAD purified from supernatants of P. gingivalis cultures was not autocitrullinated. From this they concluded that autocitrullination was a feature of cloning, which would not occur in nature. However, growing bacteria in culture is not natural either. In vivo, at the site of infection, bacteria would be lysed by the immune response and bacterial proteins, including PPAD, potentially citrullinated by PPAD itself, or by host deiminases such as PAD2, and exposed to the immune system.