Ky-anh Nguyen

Funded by: HJ & GJ Mackenzie Trust & Arthritis Australia
Recipient: Ky-anh Nguyen
Intended Department Institute Dental Research- Westmead Hospital
Project: Antibody Cross Reactive Epitope of P. gingivalis

For many centuries, there has been a suggestion that oral disease may increase the risk of acquiring (rheumatoid) arthritis – some recent epidemiological evidence supports this association. Why oral disease increases this risk is not well understood and our work seeks to explain the connection between gum disease and rheumatoid arthritis through the involvement of a particular oral bacterium implicated in gum disease.b. What questions did the grant set out to answer? What problems did you try to solve, or gaps in knowledge did you try to fill? Why is this important? Your answer should be at least 100 words. Rheumatoid arthritis is characterised by the production of antibodies which attack the body’s own protein components. The bacterium Porphyromonas gingivalis is the only oral bacteria known to be capable of producing similar protein molecules to human proteins which are targets of the auto‐ antibody response in many rheumatoid arthritis patients. It has been thought that in people with gum disease and P. gingivalis infection, an inflammatory response in the gums against this bacterium may result in the production of antibodies against the bacterial proteins that also cross‐reacts with similar proteins in human tissues in susceptible individuals, leading to progressive destruction of the joints. The missing piece to this explanation is the unknown protein targets in P. gingivalis that the auto‐antibodies in rheumatoid arthritis are directed against. This project hopes to address this gap by identifying these protein targets in P. gingivalis to confirm this mechanistic link between gum disease and rheumatoid arthritis. The bacterium Porphyromonas gingivalis has been implicated as a leading causative organism for gum disease and these patients often have elevated antibody against the organism.

We have developed a method to quantify the antibody response against the organism and have screened over 300 sera samples from rheumatoid arthritis patients to determined exposure to the bacterium. Currently, we are carrying out statistical analyses to determine whether the level of antibodyresponse to P. gingivalis correlates with various severity markers of rheumatoid arthritis.

This will inform clinicians of the need to reduce exposure to P. gingivalis through the treatment of gumdisease as part of the management strategy for rheumatoid arthritis. Using sera with high antibody titre to P. gingivalis, we have developed a technique to detect proteins from the organism that is reactive to the auto‐antibodies in these patients. From preliminary data, auto‐antibodies from each patient binds to approximately 7‐12 distinct bacterial protein targets. Currently, we are screening through the high titre sera to determine which P.gingivalis proteins are most commonly detected between different patients, thus, may represent a common risk marker for a subgroup of rheumatoid arthritis sufferers. Further work will determine the exact identity of these bacterial protein targets to confirm the mechanistic link between gum disease and rheumatoid arthritis.How might the findings inform further research to help sufferers in the future?By knowing the bacterial target(s) of the auto‐antibodies in rheumatoid arthritis, it is envisaged that a screening kit will be developed whereby a subgroup of rheumatoid patients be identified, based on their reactivity to the bacterial target(s), to require aggressive treatment for their gum disease to reduce exposure to P. gingivalis.

As auto‐antibodies are detectable in people up to 10 years before the clinical onset of rheumatoid arthritis, the early detection of anti‐P. gingivalis auto‐antibodies may allow for better prevention of RA through improved oral health or allow better control of RA treatment.The preliminary data accumulated in the study will be instrumental in securing larger national grants to continue with the work. We will complete the screen with high‐titre RA sera to compile a list of P. gingivalis proteins that are commonly reactive to auto‐antibodies in RA patients. This knowledge will be vital for the development of any future diagnostic kit to identify at‐risk patients for RA. We would like to thank Arthritis Australia and the generous gift from HJ & GJ Mackenzie Trust to support our work. It is an honour to be given the opportunity to move the research forward and we pledge to ensure the most effective use of the funds given.

  • 1m 23s

    What's the link between bad oral health and rheumatoid arthritis?