Plastic antibodies and nanoplasmonic sensors in targeting risk markers of periodontitis and systemic disorders

New diagnostic tools and preventative strategies for periodontitis and associated systemic inflammation are greatly needed both from a health and economical perspective. Due to the large numbers of individuals affected, the lack of targeted strategies to predict and prevent these diseases represents a huge gap in the healthcare product market and constitutes a substantial part of the total treatment costs of 10 billion SEK per year. The incidence of these diseases is expected to rise significantly due to growing numbers of elderly patients with natural teeth and the increased use of dental implant treatment over the past 15 years. Periodontitis is an inflammatory disease of tooth-supporting tissues affecting around 40% of the Swedish population aged over 50 years and Porphyromonas gingivalis is considered to be the major causative pathogen in the etiology of periodontal disease, mainly by expressing a high proteolytic activity through the cysteine proteases gingipains. Frequent periodontitis-induced bacteraemias involving P. gingivalis and their gingipains may induce systemic inflammation leading to e.g. cardiovascular disease (CVD) and Alzheimers disease (AD). In accordance, we have reported that gingipains in vitro modify LDL by cleaving apoB 100 and that patients with periodontitis express an atherogenic form of LDL. Furthermore, we have shown that P. gingivalis markedly increases, through gingipain activity, the expression of the CVD-risk markers TGF-β1, HGF, IGF-2 and angiopoitein 2 (Angpt2) in vascular cells. The new generation of robust, mass producible “plastic antibodies” in combination with gold nanoparticles (AuNPs) could potentially overcome limitations of existing protein biomarker detection technologies (e.g. ELISAs, RIAs or blotting techniques), and is offering an entirely new platform for protein assays or sensors analysing e.g. biomarkers of periodontitis and systemic inflammation. The main purpose of this project is to develop and test in vitro and in patients novel highly sensitive diagnostic tools based on MIPs and AuNP sensors for targeting gingipain activity and specific biomarkers for early detection of periodontitis and risk of CVD and AD.

References

- Lönn, J., Starkhammar Johansson, Kälvegren H., Brudin, L., C., Skoglund, C., Garvin, P., Särndahl, E., Ravald, N., Richter, A., Bengtsson, T.,and Nayeri, F. (2012) Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition. Results in Immunology, 2:7-12.

- Lönn, J., Starkhammar Johansson, C., Nakka, S., Palm, E., Bengtsson, T., Nayeri, F., Ravald, N. (2013) High Concentration but Low Biological Activity of Hepatocyte Growth Factor in Patients with Periodontitis. J. Periodontol. Apr 18.

- Khalaf, H., Lönn, J., Bengtsson, T. (2014) Cytokines and chemokines are differentially expressed in patients with periodontitis: possible role for TGF-beta as a marker for disease progression. Cytokine, 67:29-35.

- Zhang, B., Khalaf, H., Sirsjö, A., Bengtsson, T. (2015) Gingipains from the periodontal pathogen Porphyromonas gingivalis play a significant role in the regulation of angiopoietin 1 and angiopoietin 2 in human aortic smooth muscle cells. Infect. Immun. 83:4256-4265.